# documents

url: https://afdc.energy.gov/fuels/electricity-benefits
title: Alternative Fuels Data Center: Electric Vehicle Benefits and Considerations
scrape_date: 2025-02-28T08:32:39.529525
content_type: markdown
hash: e8d6688e5b423febe6f7c73a993efd96a95afa8759d9080ec84c373cfbb1b51f
content:
Skip to Content

![](/vite/assets/eere_header_logo-SkLjAvjd.gif)

[EERE Home](http://www.eere.energy.gov/) | [Programs & Offices](https://www.energy.gov/eere/office-energy-efficiency-renewable-energy) | [Consumer Information](https://www.energy.gov/energysaver/energy-saver)

Search the AFDC Search

[Alternative Fuels Data Center](/)

  * [Fuels & Vehicles](/fuels)

    * **[Biodiesel](/fuels/biodiesel.html)** | [Diesel Vehicles](/vehicles/diesel.html)
    * **[Electricity](/fuels/electricity.html)** | [Electric Vehicles](/vehicles/electric.html)
    * **[Ethanol](/fuels/ethanol.html)** | [Flex Fuel Vehicles](/vehicles/flexible_fuel.html)
    * **[Hydrogen](/fuels/hydrogen.html)** | [Fuel Cell Vehicles](/vehicles/fuel_cell.html)
    * **[Natural Gas](/fuels/natural_gas.html)** | [Natural Gas Vehicles](/vehicles/natural_gas.html)
    * **[Propane](/fuels/propane.html)** | [Propane Vehicles](/vehicles/propane.html)
    * **[Renewable Diesel](/fuels/renewable_diesel.html)**
    * **[Sustainable Aviation Fuel](/fuels/sustainable_aviation_fuel.html)**
    * **[Emerging Fuels](/fuels/emerging.html)**
    * **[Fuel Prices](/fuels/prices.html)**

    * [ __Alternative Fuel and Advanced Technology Vehicles](/vehicles/search/download.pdf)
    * [ __Vehicle Cost Calculator](/calc/)

  * [Conserve Fuel](/conserve)

    * [Idle Reduction](/conserve/idle-reduction-basics)
    * [Parts & Equipment](/conserve/equipment)
    * [Driving Behavior](/conserve/driving-behavior)
    * [Fleet Rightsizing](/conserve/rightsizing)
    * [System Efficiency](/conserve/system-efficiency)

    * [ __Idle Reduction Savings Worksheet](http://www.anl.gov/energy-systems/downloads/vehicle-idle-reduction-savings-worksheet)

  * [Locate Stations](/stations)

    * [Search by Location](/stations/#/find/nearest)
    * [Map a Route](/stations/#/find/route)

    * [ __Station Data by State](/stations/states)
    * [ __Download Station Data](/data_download)

  * [Laws & Incentives](/laws)

    * [Search All](/laws/search)
    * [Federal](/laws/fed_summary)
    * [State](/laws/state)
    * [Key Legislation](/laws/key_legislation)
    * [Utility Incentives](/laws/utility-incentives)

    * [ __Project Assistance & Funding Opportunities ](/project_assistance.html)
    * [ __Examples of Local Laws & Incentives ](/laws/local_examples)

  * More...

    * [Maps & Data](/data)
    * [Case Studies](/case)
    * [Publications](/publications)
    * [Tools](/tools)
    * [About](/about.html)
    * [Home](/)




  * [Maps & Data](/data)
  * [Case Studies](/case)
  * [Publications](/publications)
  * [Tools](/tools)
  * [About](/about)
  * [Home](/)



##### Print Preview

__  
Print

__  
Close

### U.S. Department of Energy - Energy Efficiency and Renewable Energy

#### Alternative Fuels Data Center

[EERE](http://www.eere.energy.gov/) » [AFDC](/) » [Fuels & Vehicles](/fuels) » [Electricity](/fuels/electricity)

  * __Printable Version



__ __ More in this section... 

  * [Electricity Basics](/fuels/electricity-basics)
  * [Benefits & Considerations](/fuels/electricity-benefits)
  * [Stations](/fuels/electricity-stations)
  * [Vehicles](/vehicles/electric)
  * [Laws & Incentives](/fuels/laws/ELEC)



# Electric Vehicle Benefits and Considerations

All forms of electric vehicles (EVs) can help improve fuel economy, lower fuel costs, and reduce emissions. Using electricity as a power source for transportation improves public health and the environment, and provides safety benefits, and contributes to a resilient transportation system.

![Photo of an electric car.](/vite/assets/73925-electricity-benefits-Dt7DXAA4.jpg)

## Public Health and the Environment

The transportation sector is the largest source of greenhouse gas emissions in the United States. A successful transition to clean transportation will require various vehicle and fuel solutions and must consider life cycle emissions. Electric and hybrid vehicles can have significant emissions benefits over conventional vehicles. All-electric vehicles produce zero tailpipe emissions, and plug-in hybrid electric vehicles (PHEVs) produce no tailpipe emissions when operating in all-electric mode. Hybrid electric vehicle (HEV) emissions benefits vary by vehicle model and type of hybrid power system.

The life cycle emissions of an electric vehicle depend on the source of the electricity used to charge it, which varies by region. In geographic areas that use relatively low-polluting energy sources for [electricity production](/fuels/electricity-production), electric vehicles typically have a life cycle emissions advantage over similar conventional vehicles running on gasoline or diesel. In regions that depend heavily on conventional electricity generation, electric vehicles may not demonstrate a strong life cycle emissions benefit. Use the [Electricity Sources and Emissions Tool](/vehicles/electric-emissions) to compare life cycle emissions of individual vehicle models in a given location.

## Batteries

The advanced batteries in electric vehicles are designed for extended life but will wear out eventually. Several manufacturers of electric vehicles are offering 8-year/100,000-mile battery warranties. [Predictive modeling](https://www.nrel.gov/docs/fy14osti/62813.pdf) by the National Renewable Energy Laboratory indicates that today’s batteries may last 12 to 15 years in moderate climates (8 to 12 years in extreme climates). In addition to climate, other factors impacting battery life include driving and charging patterns, battery cell chemistry and design, and the vehicle-battery-environment thermal system.

Check with your dealer for model-specific information about battery life and warranties. Although manufacturers have not published pricing for replacement batteries, some are offering extended warranty programs with monthly fees. If the batteries need to be replaced outside the warranty, it may be a significant expense. Battery prices are expected to continue declining as battery technologies improve and production volumes increase.

## Costs

Although energy costs for EVs are generally lower than for similar conventional vehicles, purchase prices can be significantly higher. Prices are likely to equalize with conventional vehicles, as production volumes increase and battery technologies continue to mature. Also, initial costs can be offset by fuel cost savings, [federal tax credits](/laws/ev-tax-credits), and [state and utility incentives](/laws/state). The federal [Clean Vehicle Tax Credits](https://www.irs.gov/clean-vehicle-tax-credits) are available are available to consumers, fleets, businesses, and tax-exempt entities investing in new, used, and commercial clean vehicles—including all-electric vehicles, PHEVs, fuel cell EVs—and EV charging infrastructure. Some states and electric utilities also offer incentives, many of which can be found in the [Laws and Incentives database](/laws). For more information on available incentives, [connect with your local Clean Cities and Communities coalition](https://cleancities.energy.gov/coalitions/).

Use the [Vehicle Cost Calculator](/calc/) to compare lifetime ownership costs of individual models of electric vehicles and conventional vehicles.

## Fuel Economy

Electric vehicles can reduce fuel costs dramatically because of the high efficiency of electric-drive components. Because all-electric vehicles and PHEVs rely in whole or part on electric power, their fuel economy is measured differently than that of conventional vehicles. [Miles per gallon of gasoline equivalent](/glossary#MilesperGallonofGasolineEquivalent) (MPGe) and kilowatt-hours (kWh) per 100 miles are common metrics. Depending on how they are driven, today's light-duty all-electric vehicles (or PHEVs in electric mode) can exceed 130 MPGe and can drive 100 miles consuming only 25–40 kWh. 

HEVs typically achieve better fuel economy and have lower fuel costs than similar conventional vehicles. For example, [FuelEconomy.gov](https://fueleconomy.gov/feg/Find.do?action=sbs&id=47339) lists the 2024 Toyota Corolla Hybrid at an EPA combined city-and-highway fuel economy estimate of 50 miles per gallon (MPG), while the estimate for the conventional 2024 Corolla (four cylinder, automatic) is 35 MPG. Use the [Find A Car tool](http://www.fueleconomy.gov/feg/findacar.shtml) on FuelEconomy.gov to compare fuel economy ratings of individual hybrid and conventional models.

The fuel economy of medium- and heavy-duty all-electric vehicles and PHEVs is highly dependent on the load carried and the duty cycle, but in the right applications, all-electric vehicles maintain a strong fuel-to-cost advantage over their conventional counterparts.

## Infrastructure Availability

All-electric vehicles and PHEVs have the benefit of flexible charging because the electric grid is near most locations where people park. To safely deliver energy from the electric grid to a vehicle’s battery, an EV charging station, sometimes referred to as electric vehicle supply equipment (EVSE), is needed. Drivers can charge overnight at a [residence](/fuels/electricity-charging-home), including [multifamily housing](/fuels/electricity-charging-multi), as well as the [workplace](/fuels/electricity-charging-workplace) or a [public charging](/fuels/electricity-charging-public) station when available. PHEVs have added flexibility because they can also refuel with gasoline or diesel (or possibly other fuels in the future) when necessary.

Public charging stations are not as ubiquitous as gas stations. Charging equipment manufacturers, automakers, utilities, Clean Cities and Communities coalitions, states, municipalities, and government agencies are rapidly establishing a national network of public charging stations. The number of publicly accessible charging stations in the United States reached more than 60,000 in 2024, offering more than 162,000 [charging ports](/fuels/electricity-stations#terms), according to the [Alternative Fueling Station Locator](/stations/#/find/nearest). Search for [electric charging stations](/fuels/electricity-locations) near you.

## Energy Security and Resilience

The transportation sector accounts for approximately 30% of total U.S. energy needs and 70% of U.S. petroleum consumption. Using more energy efficient vehicles like hybrid and electric vehicles supports the U.S. economy and helps diversify the U.S. transportation fleet. The multiple fuel sources used to generate electricity results in a more secure energy source for the electrified portion of the transportation sector. All of this strengthens national energy security by increasing resilience to natural disasters and fuel supply disruptions.

HEVs typically use less fuel than similar conventional vehicles because they employ electric-drive technologies to boost vehicle efficiency through regenerative braking—recapturing energy otherwise lost during braking. PHEVs and all-electric vehicles, also referred to as battery electric vehicles (BEVs), are both capable of being powered solely by electricity, which is produced in the United States from natural gas, coal, nuclear energy, wind energy, hydropower, and solar energy.

#####  ____Maps & Data

[ Light-Duty AFV, HEV, and Diesel Model Offerings, by Technology/Fuel](/data/10303)

[![Light-Duty AFV, HEV, and Diesel Model Offerings, by Technology/Fuel](/files/u/data/thumbnail/10303/generated_thumb20240522-298-njqnln.png?49ef936e34)](/data/10303)

[ U.S. Public Electric Vehicle Charging Infrastructure](/data/10972)

[![U.S. Public Electric Vehicle Charging Infrastructure](/files/u/data/thumbnail/10972/generated_thumb20240404-276-q1s3ue.png?5ac92eb07c)](/data/10972)

[ Share of All U.S. Vehicle Trips by Length (miles)](/data/10318)

[![Share of All U.S. Vehicle Trips by Length \(miles\)](/files/u/data/thumbnail/10318/generated_thumb20240123-522-oemi5x.png?924d856a41)](/data/10318)

____

[More Electricity Data](/data/keyword/electricity) | [All Maps & Data](/data)

#####  ____Case Studies

  * [__Electric School Buses Clear the Air in the Mid-Atlantic](/case/3110)
  * [__Seattle Rideshare Fleet Adds EVs, Enjoys Success](/case/3105)
  * [__EV Dollars and Sense](/case/3085)



[More Electricity Case Studies](/case/search?keyword=Electricity) | [All Case Studies](/case)

#####  ____Publications

  * [__At A Glance: Electric Vehicles](/files/u/publication/electric-drive_vehicles.pdf?46ed6d7f2c)
  * [__Electrification Futures Study: Scenarios of Electric Technology Adoption and Power Consumption for the United States](/files/u/publication/electrification_futures_study.pdf?1b3beb30d4)
  * [__Effects of Regional Temperature on Electric Vehicle Efficiency, Range, and Emissions in the United States](https://pubs.acs.org/doi/abs/10.1021/es505621s#)



[More Electricity Publications](/publications?tags\[\]=electricity) | [All Publications](/publications/)

#####  ____Tools

  * [__Laws and Incentives Search](/laws/search)
  * [__Vehicle Cost Calculator](/calc/)



[All Tools](/tools)

##### [Fuels & Vehicles](/fuels/)

  * [Biodiesel](/fuels/biodiesel)
  * [Electricity](/fuels/electricity)
  * [Ethanol](/fuels/ethanol)
  * [Hydrogen](/fuels/hydrogen)
  * [Natural Gas](/fuels/natural-gas)
  * [Propane](/fuels/propane)
  * [Renewable Diesel](/fuels/renewable-diesel)
  * [Sustainable Aviation Fuel](/fuels/sustainable-aviation-fuel)
  * [Emerging Fuels](/fuels/emerging)
  * [Fuel Prices](/fuels/prices.html)



##### [Conserve Fuel](/conserve/)

  * [Idle Reduction](/conserve/idle-reduction-basics)
  * [Parts & Equipment](/conserve/equipment)
  * [Driving Behavior](/conserve/driving-behavior)
  * [Fleet Rightsizing](/conserve/rightsizing)
  * [System Efficiency](/conserve/system-efficiency)



##### [Locate Stations](/stations)

  * [Search by Location](/stations/#/find/nearest)
  * [Map a Route](/stations/#/find/route)



##### [Laws & Incentives](/laws)

  * [Search](/laws/search)
  * [Federal](/laws/fed_summary)
  * [State](/laws/state)
  * [Key Legislation](/laws/key_legislation)
  * [Utility Incentives](/laws/utility-incentives)



##### [Data & Tools](/tools)

  * [Widgets](/widgets/)
  * [Data Downloads](/data_download/)
  * [APIs](https://developer.nrel.gov/docs/transportation)



##### [About](/about.html)

  * [Newsletters](https://www.energy.gov/eere/vehicles/vehicle-technologies-office-newsletters)


  * [Project Assistance](/project-assistance)
  * [Contacts](/contacts)



[![TRS](/vite/assets/trs-DCCuckIt.png)](mailto:technicalresponse@icf.com) **Need project assistance?**   
Email the [Technical Response Service](mailto:technicalresponse@icf.com) or call [800-254-6735](tel:800-254-6735)

  
  
The AFDC is a resource of the U.S. Department of Energy's [Vehicle Technologies Office](https://energy.gov/eere/vehicles/technology-integration).   
  
[Contacts](/contacts.html) | [Web Site Policies](https://energy.gov/about-us/web-policies) | [U.S. Department of Energy](https://energy.gov) | [USA.gov](https://www.usa.gov)

×

## 


scrape_date: 2025-02-28T08:32:39.842351
content_type: markdown
hash: 4325680a1948b985b0e83435ac781e04bb1010bbe088ffa96611fd678c69e29c
url:
https://www.quora.com/What-are-the-environmental-impacts-of-electric-vehicles-and-how-do-they-compare-to-traditional-cars

title:
What are the environmental impacts of electric vehicles, and how do they compare to traditional cars? - Quora

content:
Something went wrong. Wait a moment and try again.

Try again

Please enable Javascript and refresh the page to continue


url: http://arxiv.org/abs/2210.14908v6
scrape_date: 2025-02-28T08:40:07.706054
content_type: markdown
hash: 6688c4be3e438c7879693d73e8fe25896623f4b1c4d5c3678430f2d92c64bbe7
title:
[2210.14908v6] Powering Up a Slow Charging Market: How Do Government Subsidies Affect Charging Station Supply?

content:
Skip to main content

[![Cornell University](/static/browse/0.3.4/images/icons/cu/cornell-reduced-white-SMALL.svg)](https://www.cornell.edu/)

We gratefully acknowledge support from the Simons Foundation, [member institutions](https://info.arxiv.org/about/ourmembers.html), and all contributors. [Donate](https://info.arxiv.org/about/donate.html)

[](/IgnoreMe)

[![arxiv logo](/static/browse/0.3.4/images/arxiv-logo-one-color-white.svg)](/) > [econ](/list/econ/recent) > arXiv:2210.14908v6 

[Help](https://info.arxiv.org/help) | [Advanced Search](https://arxiv.org/search/advanced)

All fields Title Author Abstract Comments Journal reference ACM classification MSC classification Report number arXiv identifier DOI ORCID arXiv author ID Help pages Full text

Search

[![arXiv logo](/static/browse/0.3.4/images/arxiv-logomark-small-white.svg)](https://arxiv.org/)

[ ![Cornell University Logo](/static/browse/0.3.4/images/icons/cu/cornell-reduced-white-SMALL.svg) ](https://www.cornell.edu/)

open search

GO

open navigation menu

## quick links

  * [Login](https://arxiv.org/login)
  * [Help Pages](https://info.arxiv.org/help)
  * [About](https://info.arxiv.org/about)



# Economics > General Economics

**arXiv:2210.14908v6** (econ) 

[Submitted on 26 Oct 2022 ([v1](https://arxiv.org/abs/2210.14908v1)), last revised 31 Jan 2023 (this version, v6)]

# Title:Powering Up a Slow Charging Market: How Do Government Subsidies Affect Charging Station Supply?

Authors:[Zunian Luo](https://arxiv.org/search/econ?searchtype=author&query=Luo,+Z)

View a PDF of the paper titled Powering Up a Slow Charging Market: How Do Government Subsidies Affect Charging Station Supply?, by Zunian Luo

[View PDF](/pdf/2210.14908v6)

> Abstract:Electric vehicle adoption is considered to be a promising pathway for addressing climate change. However, the market for charging stations suffers from a market failure: a lack of EV sales disincentives charging station production, which in turn inhibits mass EV adoption. Charging station subsidies are often discussed as policy levers that can stimulate charging station supply and correct this market failure. Nonetheless, there is limited research examining the extent such subsidies are successful in promoting charging station supply. Using annual data on electric vehicle sales, charging station counts, and subsidy amounts from 57 California counties and a staggered difference-in-differences methodology, I find that charging station subsidies are highly effective: counties that adopt subsidies experience a 36% increase in charging station supply 2 years following subsidy adoption. This finding suggests that governmental intervention can help correct the market failure in the charging station market. 

Subjects: |  General Economics (econ.GN)  
---|---  
Cite as: | [arXiv:2210.14908](https://arxiv.org/abs/2210.14908) [econ.GN]  
  | (or  [arXiv:2210.14908v6](https://arxiv.org/abs/2210.14908v6) [econ.GN] for this version)   
  |  <https://doi.org/10.48550/arXiv.2210.14908> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Zunian Luo [[view email](/show-email/c3178241/2210.14908)]   
**[[v1]](/abs/2210.14908v1)** Wed, 26 Oct 2022 03:00:34 UTC (806 KB)  
**[[v2]](/abs/2210.14908v2)** Mon, 21 Nov 2022 03:19:54 UTC (809 KB)  
**[[v3]](/abs/2210.14908v3)** Mon, 12 Dec 2022 16:23:37 UTC (809 KB)  
**[[v4]](/abs/2210.14908v4)** Sun, 15 Jan 2023 03:48:41 UTC (809 KB)  
**[[v5]](/abs/2210.14908v5)** Sun, 29 Jan 2023 23:00:06 UTC (809 KB)  
**[v6]** Tue, 31 Jan 2023 23:10:51 UTC (809 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Powering Up a Slow Charging Market: How Do Government Subsidies Affect Charging Station Supply?, by Zunian Luo

  * [View PDF](/pdf/2210.14908v6)
  * [TeX Source](/src/2210.14908v6)
  * [Other Formats](/format/2210.14908v6)



[ ![license icon](https://arxiv.org/icons/licenses/by-4.0.png) view license ](http://creativecommons.org/licenses/by/4.0/ "Rights to this article")

Current browse context: 

econ.GN

[< prev](/prevnext?id=2210.14908&function=prev&context=econ.GN "previous in econ.GN \(accesskey p\)")   |   [next >](/prevnext?id=2210.14908&function=next&context=econ.GN "next in econ.GN \(accesskey n\)")   


[new](/list/econ.GN/new) |  [recent](/list/econ.GN/recent) | [2022-10](/list/econ.GN/2022-10)

Change to browse by: 

[econ](/abs/2210.14908?context=econ)  
[q-fin](/abs/2210.14908?context=q-fin)  
[q-fin.EC](/abs/2210.14908?context=q-fin.EC)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2210.14908)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2210.14908)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2210.14908)



[a](/static/browse/0.3.4/css/cite.css) export BibTeX citation Loading...

## BibTeX formatted citation

×

loading...

Data provided by: 

### Bookmark

[ ![BibSonomy logo](/static/browse/0.3.4/images/icons/social/bibsonomy.png) ](http://www.bibsonomy.org/BibtexHandler?requTask=upload&url=https://arxiv.org/abs/2210.14908&description=Powering Up a Slow Charging Market: How Do Government Subsidies Affect Charging Station Supply? "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2210.14908&title=Powering Up a Slow Charging Market: How Do Government Subsidies Affect Charging Station Supply? "Bookmark on Reddit")

Bibliographic Tools

# Bibliographic and Citation Tools

Bibliographic Explorer Toggle

Bibliographic Explorer _([What is the Explorer?](https://info.arxiv.org/labs/showcase.html#arxiv-bibliographic-explorer))_

Connected Papers Toggle

Connected Papers _([What is Connected Papers?](https://www.connectedpapers.com/about))_

Litmaps Toggle

Litmaps _([What is Litmaps?](https://www.litmaps.co/))_

scite.ai Toggle

scite Smart Citations _([What are Smart Citations?](https://www.scite.ai/))_

Code, Data, Media

# Code, Data and Media Associated with this Article

alphaXiv Toggle

alphaXiv _([What is alphaXiv?](https://alphaxiv.org/))_

Links to Code Toggle

CatalyzeX Code Finder for Papers _([What is CatalyzeX?](https://www.catalyzex.com))_

DagsHub Toggle

DagsHub _([What is DagsHub?](https://dagshub.com/))_

GotitPub Toggle

Gotit.pub _([What is GotitPub?](http://gotit.pub/faq))_

Huggingface Toggle

Hugging Face _([What is Huggingface?](https://huggingface.co/huggingface))_

Links to Code Toggle

Papers with Code _([What is Papers with Code?](https://paperswithcode.com/))_

ScienceCast Toggle

ScienceCast _([What is ScienceCast?](https://sciencecast.org/welcome))_

Demos

# Demos

Replicate Toggle

Replicate _([What is Replicate?](https://replicate.com/docs/arxiv/about))_

Spaces Toggle

Hugging Face Spaces _([What is Spaces?](https://huggingface.co/docs/hub/spaces))_

Spaces Toggle

TXYZ.AI _([What is TXYZ.AI?](https://txyz.ai))_

Related Papers

# Recommenders and Search Tools

Link to Influence Flower

Influence Flower _([What are Influence Flowers?](https://influencemap.cmlab.dev/))_

Core recommender toggle

CORE Recommender _([What is CORE?](https://core.ac.uk/services/recommender))_

  * Author
  * Venue
  * Institution
  * Topic



About arXivLabs 

# arXivLabs: experimental projects with community collaborators

arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website.

Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them.

Have an idea for a project that will add value for arXiv's community? [**Learn more about arXivLabs**](https://info.arxiv.org/labs/index.html).

[Which authors of this paper are endorsers?](/auth/show-endorsers/2210.14908) | [Disable MathJax](javascript:setMathjaxCookie\(\)) ([What is MathJax?](https://info.arxiv.org/help/mathjax.html)) 

  * [About](https://info.arxiv.org/about)
  * [Help](https://info.arxiv.org/help)



  * contact arXivClick here to contact arXiv [ Contact](https://info.arxiv.org/help/contact.html)
  * subscribe to arXiv mailingsClick here to subscribe [ Subscribe](https://info.arxiv.org/help/subscribe)



  * [Copyright](https://info.arxiv.org/help/license/index.html)
  * [Privacy Policy](https://info.arxiv.org/help/policies/privacy_policy.html)



  * [Web Accessibility Assistance](https://info.arxiv.org/help/web_accessibility.html)
  * [arXiv Operational Status ](https://status.arxiv.org)  
Get status notifications via [email](https://subscribe.sorryapp.com/24846f03/email/new) or [slack](https://subscribe.sorryapp.com/24846f03/slack/new)


title: Are Electric Cars Better for the Environment? — Lectron EV
scrape_date: 2025-02-28T08:40:09.027398
content_type: markdown
hash: 89b6b806564f9fd66adc5ab97147e1f286c108ad8f7a96ec56c9b2bdc0ef09d9
url:
https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment?srsltid=AfmBOoowe8Oi-eg0BrFoJmZqIcq3ylqwI6RX3pOQ2lg-Nd825hobCLJE

content:
Skip to content

[](https://ev-lectron.com/)

FREE SHIPPING ON ORDERS $35+ 

FREE SHIPPING ON ORDERS $35+ 

Menu

[ ![Lectron EV](//ev-lectron.com/cdn/shop/files/lectron_final_files_360x160_361x160_430c7d96-93b4-45c8-a7aa-6b6f972bb9f9_361x160.png?v=1723429460) ](/)

Cancel 

  * [ Login  ](https://ev-lectron.com/customer_authentication/redirect?locale=en®ion_country=US)



[ View cart ](/cart)

  * EV Chargers 
    * [ Level 1 EV Chargers ](/collections/level-1-ev-chargers)
    * [ Level 2 EV Chargers ](/collections/level-2-ev-chargers)
  * [ EV Adapters ](/collections/ev-adapters)
  * Tesla 
    * [ Tesla Chargers ](/collections/tesla-chargers)
    * [ Tesla Adapters ](/collections/tesla-adapters)
    * [ Tesla Cable Organizers ](/collections/tesla-cable-organizers)
    * [ Tesla Bundles ](/collections/tesla-bundles)
  * J1772 
    * [ J1772 Chargers ](/collections/j1772-chargers)
    * [ J1772 Adapters ](/collections/j1772-adapters)
    * [ J1772 Mounts ](/collections/j1772-mounts)
    * [ J1772 Bundles ](/collections/j1772-bundles)
  * NEMA Plugs 
    * [ NEMA 5-15 ](/collections/nema-5-15)
    * [ NEMA 10-30 ](/collections/nema-10-30)
    * [ NEMA 14-50 ](/collections/nema-14-50)
  * [ V-BOX ](/collections/v-box)
  * [ Socket Splitter ](/collections/socket-splitter)
  * [ Bundle & Save ](/collections/special-bundles)
  * [ Blog ](/blogs/blog)
  * [ Buyer's Guide ](https://ev-lectron.com/pages/buyers-guide)
  * [ Test Our Products ](/pages/test-products)



  * [ Login  ](https://ev-lectron.com/customer_authentication/redirect?locale=en®ion_country=US)

Close

  * [ EV Chargers ](/collections/ev-chargers)

EV Chargers

    * [ Level 1 EV Chargers ](/collections/level-1-ev-chargers)
    * [ Level 2 EV Chargers ](/collections/level-2-ev-chargers)
  * [ EV Adapters ](/collections/ev-adapters)
  * [ Tesla ](/collections/tesla)

Tesla

    * [ Tesla Chargers ](/collections/tesla-chargers)
    * [ Tesla Adapters ](/collections/tesla-adapters)
    * [ Tesla Cable Organizers ](/collections/tesla-cable-organizers)
    * [ Tesla Bundles ](/collections/tesla-bundles)
  * [ J1772 ](/collections/j1772-owners)

J1772

    * [ J1772 Chargers ](/collections/j1772-chargers)
    * [ J1772 Adapters ](/collections/j1772-adapters)
    * [ J1772 Mounts ](/collections/j1772-mounts)
    * [ J1772 Bundles ](/collections/j1772-bundles)
  * [ NEMA Plugs ](/collections/nema-plugs)

NEMA Plugs

    * [ NEMA 5-15 ](/collections/nema-5-15)
    * [ NEMA 10-30 ](/collections/nema-10-30)
    * [ NEMA 14-50 ](/collections/nema-14-50)
  * [ V-BOX ](/collections/v-box)
  * [ Socket Splitter ](/collections/socket-splitter)
  * [ Bundle & Save ](/collections/special-bundles)
  * [ Blog ](/blogs/blog)
  * [ Buyer's Guide ](https://ev-lectron.com/pages/buyers-guide)
  * [ Test Our Products ](/pages/test-products)



![Are Electric Cars Better for the Environment?](//ev-lectron.com/cdn/shop/articles/Blog__are_electric_cars_better_for_the_environment_RE_201223_Banner_V1-454554_1200x361_crop_center.jpg?v=1703120202) ![Are Electric Cars Better for the Environment?](//ev-lectron.com/cdn/shop/articles/Blog__are_electric_cars_better_for_the_environment_RE_201223_Banner_V1-454554_1200x361_crop_center.jpg?v=1703120202)

Share: 

[ Share on Facebook ](//www.facebook.com/sharer.php?u=https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment) [ Tweet on Twitter ](//twitter.com/share?url=https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment) [ Share on LinkedIn ](//www.linkedin.com/shareArticle?mini=true&url=https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment&title=Are%20Electric%20Cars%20Better%20for%20the%20Environment?) [ Pin on Pinterest ](//pinterest.com/pin/create/button/?url=https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment&media=//ev-lectron.com/cdn/shop/articles/Blog__are_electric_cars_better_for_the_environment_RE_201223_Banner_V1-454554_1024x.jpg?v=1703120202&description=Are%20Electric%20Cars%20Better%20for%20the%20Environment?)

December 20, 2023  Joel Manansala 

#  Are Electric Cars Better for the Environment? 

By the year 2035, the federal government is looking to ban the sales of new gasoline-powered cars in an effort to achieve zero emissions by 2050. To further promote e-mobility, the Biden administration, through the Inflation Reduction Act of 2022, is incentivizing converts by giving tax credits to lower the cost of purchasing a new or used electric vehicle (EV) – both battery-electric and plug-in hybrid models.

But how "clean" really are EVs?

![](https://cdn.shopify.com/s/files/1/2948/6296/files/pexels-mike-bird-110844_480x480.jpg?v=1702519743)

## What are EVs, and how do they work?

Electric vehicles are automobiles powered by electric motors rather than internal combustion engines. Unlike gas-powered cars that run by burning fuel, EVs rely on electricity stored in lithium-ion batteries for energy. When driving, the electric motor uses power from the batteries to propel the vehicle forward. EVs can be charged at home, through public charging stations, or high-speed charging stations.

[Learn more on How do Electric cars work in our article](https://ev-lectron.com/blogs/blog/how-do-electric-cars-work).

## What are the different kinds of EVs?

There are three main types of EVs:

  1. **Battery Electric Vehicles (BEVs):** Pure electric vehicles that run solely on electricity stored in large batteries.

  2. **Plug-in Hybrid Electric Vehicles (PHEVs):** Plug-in hybrids combine an internal combustion engine with a battery, allowing for both electric and gasoline-powered driving.

  3. **Hybrid Electric Vehicles (HEVs):** Uses a combination of an internal combustion engine and an electric motor but cannot be plugged in for recharging.




## How does electric car production affect the environment? 

While electric vehicles are lauded for their eco-friendly operation, the EV production process does have environmental consequences. The extraction and processing of raw materials for electric vehicle batteries, such as lithium and cobalt, can result in habitat disruption and resource depletion. Additionally, manufacturing EV batteries and electric motors requires energy, often sourced from fossil fuels.

![](https://cdn.shopify.com/s/files/1/2948/6296/files/img-1_480x480_4e108c52-595a-4319-b7c3-6562eeeb000c_480x480.webp?v=1702519816)

However, scientists and car manufacturers have been looking into incorporating recycled raw materials, including valuable metals, in the battery production process. On average, [EV batteries can last between 8 to 10 years or 100,000 to 200,000 miles](https://ev-lectron.com/blogs/blog/how-long-do-electric-car-batteries-last "EV batteries can last between 8 to 10 years or 100,000 to 200,000 miles"), but some can last longer than the entire life cycle of the EV itself. After the batteries have served their intended purpose, recycling facilities will collect, discharge, dismantle, shred, sort, and refine materials for reuse. The refined materials are used in the production of new batteries or other products, completing the recycling loop.

## Benefits of electric cars on the environment

Despite the production-related environmental impacts, electric cars offer several benefits:

  1. **Slowing Climate Change:** One of the primary advantages of EVs is their contribution to reducing the emission of greenhouse gases. By relying on electricity, which can be generated from renewable sources like solar or wind power, EVs leave a smaller carbon footprint compared to traditional gasoline vehicles.

  2. **Reducing Local Air Pollution:** Electric cars produce zero tailpipe emissions, improving air quality in urban areas. Traditional vehicles emit pollutants like nitrogen oxides and particulate matter, contributing to respiratory problems and smog. The shift to electric vehicles helps combat these issues.

  3. **Less Waste Through Recycling:** [Electric car battery recycling](https://ev-lectron.com/blogs/blog/recycling-electric-car-batteries "Electric car battery recycling") is a key element in minimizing the environmental impact of EVs. As the industry advances, efficient recycling methods for lithium-ion batteries are being developed, reducing the amount of waste generated from the disposal of used batteries.




## Four ways that EVs are better for the environment

![](https://cdn.shopify.com/s/files/1/2948/6296/files/pexels-kelly-4394341_600x600.jpg?v=1702519877)

**Reduced Carbon Emissions**

The significant reduction in greenhouse gas emissions from electric vehicles stems from their unique mode of propulsion. Unlike a traditional gasoline car, an electric vehicle produces fewer emissions. The absence of exhaust emissions, particularly carbon dioxide (CO2) and other pollutants associated with burning fossil fuels, is a crucial factor in mitigating climate change. By opting for electric power, EVs directly contribute to lowering the concentration of greenhouse gases in the atmosphere, thereby slowing the pace of global warming and its associated adverse effects on ecosystems and weather patterns.

**Energy Efficiency**

The inherent efficiency of electric motors is a game-changer in the quest for sustainable transportation. Electric motors boast a higher energy conversion efficiency compared to internal combustion engines. When energy is drawn from the vehicle's power source, be it a battery or a plug-in hybrid system, a more significant proportion of that energy is utilized to propel the vehicle. This increased efficiency translates into less energy waste, reducing the overall demand for electricity and, consequently, the environmental impact associated with energy production. This efficiency is a key element in making EVs a greener alternative to traditional vehicles.

**Noise Pollution Reduction**

Electric vehicles contribute to a quieter and more serene urban environment due to their near-silent operation. A gas-powered car with an internal combustion engine generates noise through an exhaust system, engine combustion, and mechanical components. In contrast, an EV, propelled by an electric motor, produces minimal noise during operation. This reduction in noise pollution has significant implications for the well-being of urban residents. Quieter streets contribute to improved mental health, reduced stress levels, and an overall enhancement of the urban living experience.

**Lower Dependence on Fossil Fuels**

As electric vehicles become more prevalent, there is a simultaneous push for a transition in the energy grid from fossil fuels to renewable sources. The electricity used to charge EVs can be sourced from renewable energy, such as solar, wind, or hydropower. This shift is crucial in addressing the environmental impact of traditional vehicles, which rely heavily on fossil fuels and other natural gas sources. By decreasing the dependence on non-renewable resources, EVs play a pivotal role in fostering a more sustainable and eco-friendly energy ecosystem. This transition is not only beneficial for reducing carbon dioxide emissions but also contributes to energy security and resilience against the finite nature of fossil fuel resources.

## Electric vs. Petrol Car

![](https://cdn.shopify.com/s/files/1/2948/6296/files/Electric-Cars-vs.-Gas-Cars-A-Cost-Comparison_Square_8e477415-6158-4ed7-9c0b-3af897d269f7_480x480.jpg?v=1702519921)

To truly know which one is better for the environment, let's have a look at the major differences between electric and petrol cars:

  1. **Emissions and Environmental Impact:**

     * **Electric Cars:** EVs emit zero tailpipe emissions during operation, helping reduce carbon emissions, especially when charged using renewable energy sources. However, EV battery production also creates upstream emissions.

     * **Petrol Cars:** Conventional vehicles emit pollutants such as carbon dioxide (CO2), nitrogen oxides (NOx), and particulate matter during combustion, contributing to air pollution and climate change.

  2. **Operating Costs:**

     * **Electric Cars:** EVs generally have lower operating costs per mile/kilometer due to the efficiency of electric motors, fewer moving parts, and lower maintenance requirements. Electricity is often cheaper than petrol.

     * **Petrol Cars:** An average new gasoline car may have higher fuel and maintenance costs over the vehicle's lifetime, as petrol prices can vary, and internal combustion engines have more components that can wear out.

  3. **Performance:**

     * **Electric Cars:** EVs provide instant torque, resulting in quick acceleration and a smooth driving experience. Electric motors often offer a more responsive and quiet operation.

     * **Petrol Cars:** ICE cars offer a wide range of performance options, from fuel-efficient models to high-performance sports cars. However, internal combustion engines may have a brief lag in power delivery.

  4. **Range and Charging:**

     * **Electric Cars:** EV driving range can vary, but advancements in battery technology are increasing it. EV charging infrastructure is expanding, with options for home charging, public charging stations, and fast charging networks.

     * **Petrol Cars:** Gas cars generally have a longer driving range per tank of fuel, and refueling at petrol stations is quick. However, the infrastructure is already established, whereas electric charging infrastructure is still developing.

  5. **Infrastructure and Convenience:**

     * **Electric Cars :** EVs require a charging infrastructure, which is expanding but may not be as ubiquitous as petrol stations. Home charging is convenient for many EV owners.

     * **Petrol Cars:** ICE vehicles benefit from a well-established network of petrol stations, offering widespread accessibility for refueling.

  6. **Government Incentives:**

     * **Electric Cars:** In many regions, governments offer incentives such as tax credits, rebates, or reduced registration fees to encourage the adoption of electric vehicles. Additionally, the expanded Inflation Reduction Act grants incentives to anyone who installs qualified charging equipment. The Federal Tax Credit gives individuals 30% off [Lectron home charging stations](https://ev-lectron.com/collections/v-box) plus installation costs (up to $1,000).

     * **Petrol Cars:** Typically do not receive specific incentives related to fuel type, as they are the traditional vehicle type.

  7. **Vehicle Variety:**

     * **Electric Cars:** Offer a growing variety of models, including sedans, SUVs, and even trucks. The market is expanding as technology advances.

     * **Petrol Cars:** Have a wide range of models, sizes, and types, providing extensive options for consumers.

  8. **Resale Value:**

     * **Electric Cars:** Historically, EVs have faced concerns about resale value due to rapid advancements in battery technology. However, this trend is changing as batteries become more durable and warranties improve.

     * **Petrol Cars:** Generally, resale values are influenced by factors such as brand reputation, model popularity, and overall condition.




## Are hybrid cars just as good for the environment?

In the context of [hybrid vs electric car](https://ev-lectron.com/blogs/blog/hybrid-vs-electric-car-whats-the-difference), although hybrid vehicles are known for their enhanced fuel efficiency, they fall short in environmental benefits when compared to pure electric vehicles. This is due to hybrids' dependence on internal combustion engines, which makes them less efficient in lowering greenhouse gas emissions and carbon pollution than their fully electric counterparts.

## FAQs

  * Can Electric Vehicles Cut Pollution?

Yes, electric vehicles can cut pollution significantly. By relying on electricity, which can be generated from renewable sources, EVs produce fewer emissions compared to traditional vehicles, reducing both air pollution and greenhouse gas emissions.



  * What are the disadvantages of electric cars on the environment?

The main disadvantages include the environmental impact of battery production, extraction of raw materials, and energy sourcing for manufacturing. However, ongoing advancements in technology and recycling methods aim to address these concerns.



  * Are electric cars better for the environment?

Overall, electric cars are better for the environment when considering their operational benefits, such as reduced emissions and energy efficiency. However, it's essential to address the environmental impacts associated with their production and disposal. Even after taking battery manufacture into consideration, electric cars are still the more environmentally friendly option.



  * Does cold weather affect EV cars?

Cold weather can affect the range of electric vehicles due to the impact on battery performance. Batteries may experience reduced efficiency in low temperatures, leading to a temporary decrease in driving range. However, advancements in battery technology are continuously improving EV performance in various weather conditions.




Share: 

[ Share on Facebook ](//www.facebook.com/sharer.php?u=https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment) [ Tweet on Twitter ](//twitter.com/share?url=https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment) [ Share on LinkedIn ](//www.linkedin.com/shareArticle?mini=true&url=https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment&title=Are%20Electric%20Cars%20Better%20for%20the%20Environment?) [ Pin on Pinterest ](//pinterest.com/pin/create/button/?url=https://ev-lectron.com/blogs/blog/are-electric-cars-better-for-the-environment&media=//ev-lectron.com/cdn/shop/articles/Blog__are_electric_cars_better_for_the_environment_RE_201223_Banner_V1-454554_1024x.jpg?v=1703120202&description=Are%20Electric%20Cars%20Better%20for%20the%20Environment?)

[ Previous article  What is the Tesla Model Y Battery Capacity?  ](/blogs/blog/what-is-the-tesla-model-y-battery-capacity)

##  Main Menu 

  * [ EV Chargers ](/collections/ev-chargers)
  * [ EV Adapters ](/collections/ev-adapters)
  * [ Tesla ](/collections/tesla)
  * [ J1772 ](/collections/j1772-owners)
  * [ NEMA Plugs ](/collections/nema-plugs)
  * [ V-BOX ](/collections/v-box)
  * [ Socket Splitter ](/collections/socket-splitter)
  * [ Bundle & Save ](/collections/special-bundles)
  * [ Blog ](/blogs/blog)
  * [ Buyer's Guide ](https://ev-lectron.com/pages/buyers-guide)
  * [ Test Our Products ](/pages/test-products)



##  Get To Know Us 

  * [ About Lectron ](/pages/about-us)
  * [ Business Inquiries ](/pages/business-inquiries)
  * [ Affiliate Program ](/pages/lectron-electric-vehicle-affiliate-program)
  * [ Buy Wholesale ](/pages/buy-wholesale-with-lectron)
  * [ Tax Rebates & Incentives ](https://ev-lectron.com/pages/tax-rebate)
  * [ Press ](/blogs/news)
  * [ Test Our Products ](/pages/test-products)
  * [ Suggestion Box ](https://ev-lectron.com/pages/product-suggestion)



##  Support 

  * [ Contact Us ](https://ev-lectron.com/pages/contact-us)
  * [ Shipping Policy ](https://ev-lectron.com/pages/shipping-policy)
  * [ Warranty ](https://ev-lectron.com/pages/refund-policy)
  * [ Terms of Service ](https://ev-lectron.com/pages/terms-of-service)
  * [ Privacy Policy ](https://ev-lectron.com/pages/privacy-policy)
  * [ User Manuals ](https://ev-lectron.com/pages/user-manuals?_pos=1&_sid=e2e835650&_ss=r)
  * [ Firmware ](https://ev-lectron.com/pages/firmware)
  * [ V-Box Pro Q&A; ](/pages/v-box-pro-q-a)



##  Follow us 

[ Find us on Facebook ](https://www.facebook.com/lectronev "Facebook") [ Find us on Instagram ](https://www.instagram.com/lectronev/ "Instagram") [ Find us on LinkedIn ](https://www.linkedin.com/company/lectronev/?viewAsMember=true "LinkedIn") [ Find us on YouTube ](https://www.youtube.com/channel/UChO5lmO_AaV39Ey3wJ6adrA "YouTube")

Copyright (C) 2025 Lectron EV. 

[Powered by Shopify](https://www.shopify.com?utm_campaign=poweredby&utm_medium=shopify&utm_source=onlinestore)

"american_express" 
  * American Express
"apple_pay" 
  * Apple Pay
"diners_club" 
  * Diners Club
"discover" 
  * Discover
"google_pay" 
  * Google Pay
"master" 
  * Mastercard
"paypal" 
  * PayPal
"shopify_pay" 
  * Shop Pay
"venmo" 
  * Venmo
"visa" 
  * Visa



##  Added to your cart: 

## 

** total_quantity ** | ** unit_price ** / ** unit_measure ** 

  * (-) 



Cart subtotal 

[ View cart () ](/cart) Checkout

![Lectron EV](https://px.ads.linkedin.com/collect/?pid=4423124&fmt=gif)


url: https://www.epa.gov/greenvehicles/electric-vehicle-myths
title: Electric Vehicle Myths | US EPA
scrape_date: 2025-02-28T08:55:32.161403
content_type: markdown
hash: 2c0ceb2f179f7772b6f584e4038f48721c8aa8328fc6068e3d6f1c7958d71d93
content:
Skip to main content

![U.S. flag](/themes/epa_theme/images/us_flag_small.png)

An official website of the United States government

Here’s how you know

Here’s how you know

![Dot gov](/themes/epa_theme/images/icon-dot-gov.svg)

**Official websites use .gov**   
A **.gov** website belongs to an official government organization in the United States. 

![HTTPS](/themes/epa_theme/images/icon-https.svg)

**Secure .gov websites use HTTPS**   
A **lock** (LockA locked padlock) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites. 

JavaScript appears to be disabled on this computer. Please [click here to see any active alerts](/alerts).

[ ](/ "Home") Menu

Search Search

Primary navigation

  * Environmental Topics 
    * [Environmental Topics](/environmental-topics)
    * [Air](/environmental-topics/air-topics)
    * [Bed Bugs](/bedbugs)
    * [Cancer](/environmental-topics/epa-efforts-reduce-exposure-carcinogens-and-prevent-cancer)
    * [Chemicals, Toxics, and Pesticide ](/environmental-topics/chemicals-pesticides-and-toxics-topics)
    * [Emergency Response](/emergency-response)
    * [Environmental Information by Location ](/environmental-topics/environmental-information-by-location)
    * [Greener Living](/environmental-topics/greener-living)
    * [Health](/environmental-topics/health-topics)
    * [Land, Waste, and Cleanup](/environmental-topics/land-waste-and-cleanup-topics)
    * [Lead](/lead)
    * [Mold](/mold)
    * [Radon](/radon)
    * [Research](/research)
    * [Science Topics](/environmental-topics/science-topics)
    * [Water Topics](/environmental-topics/water-topics)
    * [A-Z Topic Index](/topics-epa-web)
  * Laws & Regulations 
    * [Laws & Regulations](/laws-regulations "View links to regulatory information by topic and sector, and to top pages about environmental laws, regulations, policies, compliance, and enforcement")
    * [By Business Sector](/regulatory-information-sector)
    * [By Topic](/regulatory-information-topic)
    * [Compliance](/compliance)
    * [Enforcement](/enforcement)
    * [Laws and Executive Orders](/laws-regulations/laws-and-executive-orders)
    * [Regulations](/laws-regulations/regulations)
  * Report a Violation 
    * [Report a Violation](/report-violation)
    * [Environmental Violations](https://echo.epa.gov/report-environmental-violations)
    * [Fraud, Waste or Abuse](https://www.epaoig.gov/epa-oig-hotline-complaint-form)
  * About EPA 
    * [About EPA](/aboutepa)
    * [Our Mission and What We Do](/aboutepa/our-mission-and-what-we-do)
    * [Headquarters Offices](/aboutepa#hq)
    * [Regional Offices](/aboutepa/regional-and-geographic-offices)
    * [Labs and Research Centers](/aboutepa/research-centers-programs-and-science-advisory-organizations)
    * [Planning, Budget, and Results](/planandbudget)
    * [Organization Chart](/aboutepa/epa-organization-chart)
    * [EPA History](/history)
    * [Staff Directory](https://cfpub.epa.gov/locator/index.cfm)



## Breadcrumb

  1. [Home](/)
  2. [Green Vehicle Guide](/greenvehicles)
  3. [Learn About Green Vehicles](/greenvehicles/learn-about-green-vehicles)



#  Electric Vehicle Myths 

[ ![Sign up](/system/files/styles/thumbnail/private/images/2023-08/subscribe-small.png?itok=XlxMSzcc) ](/greenvehicles/forms/green-vehicle-guide-e-updates)

[Sign up for  
E-Updates](/greenvehicles/forms/green-vehicle-guide-e-updates)

 

[EV Video Challenge](/greenvehicles/ev-video-challenge-winners)  
Winner Highlight

**On this page:**

  * Myth #1: Electric vehicles are worse for the climate than gasoline cars because of power plant emissions.
  * Myth #2: Electric vehicles are worse for the climate than gasoline cars because of battery manufacturing.
  * Myth #3: Electric vehicle batteries are unreliable and need to be replaced every few years.
  * Myth #4: The increase in electric vehicles entering the market will collapse the U.S. power grid.
  * Myth #5: There is nowhere to charge.
  * Myth #6: Electric vehicles don’t have enough range to handle daily travel demands.
  * Myth #7: Electric vehicles are not as safe as comparable gasoline vehicles.



## EV Facts

### Myth #1: Electric vehicles are worse for the climate than gasoline cars because of power plant emissions.

> ### FACT: Electric vehicles (EVs) typically have a smaller carbon footprint than gasoline cars, even when accounting for the electricity used for charging, plus they are far more efficient when it comes to energy use.

Electric vehicles (EVs) have no tailpipe emissions. Generating the electricity used to charge EVs, however, may create carbon pollution. The amount varies widely based on how local power is generated, e.g., using coal or natural gas, which emit carbon pollution, versus renewable resources like wind or solar, which do not. Even accounting for these electricity emissions, research shows that an EV is typically responsible for lower levels of greenhouse gases (GHGs) than an average new gasoline car. To the extent that more renewable energy sources like wind and solar are used to generate electricity, the total GHGs associated with EVs could be even lower. (In 2020, renewables became the second-most prevalent U.S. electricity source.1 ) Learn more about electricity production in your area by visiting [EPA’s Power Profiler interactive](/egrid/power-profiler#/) web page. By simply inputting your zip code, you can find the energy mix in your region.

A significant advantage of EVs compared to conventional gasoline vehicles is their energy efficiency. EVs use approximately 87%–91% of the energy from the battery and regenerative braking to propel the vehicle. Gasoline vehicles only convert about 16–25% of the energy from gasoline into movement (averaging highway and city driving).2

EPA and Department of Energy's (DOE’s) [Beyond Tailpipe Emissions Calculator](https://www.fueleconomy.gov/feg/Find.do?action=bt2) can help you estimate the greenhouse gas emissions associated with charging and driving an EV or a plug-in hybrid electric vehicle (PHEV) where you live. You can select an EV or PHEV model and type in your zip code to see the CO2 emissions and how they stack up against those associated with a gasoline car.

### Myth #2: Electric vehicles are worse for the climate than gasoline cars because of battery manufacturing.

> ### FACT: The greenhouse gas emissions associated with an electric vehicle over its lifetime are typically lower than those from an average gasoline-powered vehicle, even when accounting for manufacturing.

Some studies have shown that making a typical EV can create more carbon pollution than making a gasoline car. This is because of the additional energy required to manufacture an EV’s battery. Still, over the lifetime of the vehicle, total GHG emissions associated with manufacturing, charging, and driving an EV are typically lower than the total GHGs associated with a gasoline car. That’s because EVs have zero tailpipe emissions and are typically responsible for significantly fewer GHGs during operation (see Myth 1 above).

For example, researchers at Argonne National Laboratory estimated emissions for both a gasoline car and an EV with a 300-mile electric range. In their estimates, while GHG emissions from EV manufacturing and end-of-life are higher (shown in orange below), total GHGs for the EV are still lower than those for the gasoline car.

![Bar charts showing lifecycle GHGs for an electric vehicle and a gas car](/system/files/styles/large/private/images/2022-06/lifecycle-ghgs-ev-gas-cars-670px.png?itok=2RCNUe6A)

Estimates shown3 from [GREET 2 2021](https://greet.es.anl.gov/) are intended to be illustrative only. Estimates represent model year 2020. Emissions will vary based on assumptions about the specific vehicles being compared, EV battery size and chemistry, vehicle lifetimes, and the electricity grid used to recharge the EV, among other factors.

Above, the blue bar represents emissions associated with the battery. The orange bars encompass the rest of the vehicle manufacturing (e.g., extracting materials, manufacturing and assembling other parts, and vehicle assembly) and end-of-life (recycling or disposal). The gray bars represent upstream emissions associated with producing gasoline or electricity (U.S. mix), and the yellow bar shows tailpipe emissions during vehicle operations.

Recycling EV batteries can reduce the emissions associated with making an EV by reducing the need for new materials. While some challenges exist today, research is ongoing to improve the process and rate of EV battery recycling. For more information on EV battery development and recycling, visit:

  * U.S. Department of Energy’s [ReCell Center](https://www.anl.gov/article/doe-launches-its-first-lithiumion-battery-recycling-rd-center-recell)
  * [National Blueprint for Lithium Batteries, 2021-2030 (pdf)](https://www.energy.gov/sites/default/files/2021-06/FCAB%20National%20Blueprint%20Lithium%20Batteries%200621_0.pdf) (1.6 MB, June 2021, report published by the Federal Consortium for Advanced Batteries)



### Myth #3: Electric vehicle batteries are unreliable and need to be replaced every few years.

> ### FACT: Electric vehicle battery replacements due to failures are uncommon.

Unlike starter batteries used in gasoline vehicles, electric vehicle drivetrain batteries are designed to last the lifetime of the vehicle and recent data shows they have very low failure rates. A recent study of about 15,000 vehicles from the earliest models through model year 2023 showed that electric vehicle battery replacements due to failure have been rare, at an average of 2.5%, outside of major recalls.4 Vehicle and battery technologies have improved since 2010, when modern EVs first entered the market, and since model year 2016 they have had less than a 0.5% failure rate. The majority of these batteries would have been covered as part of the manufacturer's warranty.

![Bar chart of EV battery replacements due to failure, model year 2011-2023. Share of batteries that failed peaked in 2011 at 7.5%. In 2012, it was a 3.6% failure rate. In 2013, it was 4.4%. In 2014, it was 3.9%. In 2015, it was 1.6%. In 2016, it was 0.3%. In 2017, it was 0.1%.  In 2018, it was 0.4%. In 2019, it was 0.2%. In 2020, it was 0.1%. In 2021, it was 0.5%. In 2022, it was 0.3%. And in 2023, it was 0.1%.](/system/files/styles/large/private/images/2024-06/pev-battery-replacements.png?itok=awIQPVGG)

                                                                                               (Source: [U.S. DOE](https://www.energy.gov/eere/vehicles/articles/fotw-1339-april-22-2024-plug-electric-vehicle-battery-replacements-due), citing [Recurrent, 2023](https://www.recurrentauto.com/research/how-long-do-ev-batteries-last))

**Note:** Does not include EV battery recall replacements. Plug-in vehicles include all-electric and plug-in hybrid electric vehicles.

Batteries do tend to lose some of their initial range over time, but this study found that 97.5% of EVs are still using their original batteries (outside major recalls), and the replacement rate falls to under one percent for EVs made from 2016 onward. Current batteries and technologies have vastly improved since 2010, with expectations to improve performance and reliability while reducing impacts to the environment. [Visit Department of Energy’s Vehicle Technologies Office to learn about the future of EV batteries](https://www.energy.gov/eere/vehicles/batteries).

### Myth #4: The increase in electric vehicles entering the market will collapse the U.S. power grid.

> ### FACT: Electric vehicles have charging strategies that can prevent overloading the grid, and, in some cases, support grid reliability.

It is true that the increasing number of electric vehicles on the road will lead to increased electricity demand. Yet, how that impacts the grid will depend on several factors, such as the power level and time of day when vehicles are charged, and the potential for vehicle-to-grid (V2G) charging 5 among others.

  * **EVs can be charged at off-peak times** , such as overnight, when rates are often cheaper. Even with a mix of charging times (so not all nighttime charging), research indicates that sufficient capacity will exist to cover EVs entering the market in the coming years.6 And further down the road, when renewables make up a larger part of our energy mix in many regions, switching to more daytime charging (when some renewables like solar generate energy) with some energy storage capability should allow the grid to handle increases in EV charging.7 California leads the country with more than 1 million electric vehicles and EV charging currently makes up less than 1% of the state’s grid total load, even during peak hours.8
  * **EV charging consumed less electricity than water heating and air conditioning** in a typical U.S. household in 2020, according to recent data released by the U.S. Energy Information Agency. 9
  * **Vehicle-to-grid (V2G) charging** allows EVs to act as a power source that may help with grid reliability by pushing energy back to the grid from an EV battery. This is done by allowing EVs to charge when electricity demand is low and drawing on them when that demand is high.



Long term, higher electricity demand from EV growth may drive the need for upgrades to transmission and distribution infrastructure. Planning for this possibility is underway. The Department of Energy’s (DOE) [Build a Better Grid Initiative](https://www.energy.gov/articles/biden-harris-administration-announces-13-billion-modernize-and-expand-americas-power-grid), launched as part of the Bipartisan Infrastructure Law, will provide over $13 billion towards improving the reliability and efficiency of the grid over the next decade. Visit DOE’s [Bipartisan Infrastructure Programs](https://www.energy.gov/bil/bipartisan-infrastructure-law-programs-department-energy) and search “grid infrastructure” to see where the initial investments will be made.

### Myth #5: There is nowhere to charge.

> ### FACT: Electric vehicles can be plugged into the same type of outlet as your toaster! When you need to charge while on the road, you’ll find over 75,000 stations and 207,000 EV charging ports in the U.S. available to the public.

Many people can meet their driving needs by plugging in only at home. Most EVs can be charged with a standard 120 Volt (Level 1) outlet. To charge the vehicle more quickly, you can install a dedicated 240 Volt (Level 2) outlet or charging system. And for those who live in apartments or condominiums, EV charging stations are becoming a more common building amenity.

Access to EV charging will increase significantly in the coming years as a result of government initiatives put in place as part of the [Bipartisan Infrastructure Law](https://www.energy.gov/articles/president-biden-doe-and-dot-announce-5-billion-over-five-years-national-ev-charging#:~:text=%E2%80%9CThe%20Bipartisan%20Infrastructure%20Law%20is,coast-to-coast.%E2%80%9D), including an investment of up to $7.5 billion to build out a national network of electric vehicle chargers along highways, and in communities and neighborhoods. For the most current charger data, the Joint Office of Energy and Transportation tracks the continuous [growth of EV chargers](https://driveelectric.gov/stations-growth) over time. For up-to-date information on EV charging locations, visit their [Electric Vehicle Charging Stations](https://driveelectric.gov/stations) map.

Interested in seeing how many chargers may be needed in your area? Use DOE’s [EV Pro Lite Tool](https://afdc.energy.gov/evi-pro-lite) to get an estimate on charging needs in your state or metropolitan area as EV adoption grows.

### Myth #6: Electric vehicles don’t have enough range to handle daily travel demands.

> ### FACT: Electric vehicle range is more than enough for typical daily use in the U.S.

EVs have sufficient range to cover a typical household’s daily travel. In 2022, according to the National Household Travel Survey, over 73% of all on-road passenger trips were 10 miles or less, and over 98% were less than 75 miles.10 Today, most EV models go above 200 miles on a fully-charged battery, with all new models rated for more than 100 miles on a single charge. And automakers have announced plans to release even more long-range models in the coming years.

Range estimates for specific EVs are available from the [Find A Car tool](https://www.fueleconomy.gov/feg/findacar.shtml) — click on the car you are interested in, and check out the “EPA Fuel Economy” line in the table.

How you drive your vehicle and the driving conditions, including hot and cold weather, also affect the range of an EV; for instance, researchers found on average range could decrease about 40% due to cold temperatures and the use of heat.11

### Myth #7: Electric vehicles are not as safe as comparable gasoline vehicles.

> ### FACT: Electric vehicles must meet the same safety standards as conventional vehicles.

All light duty cars and trucks sold in the United States must meet the [Federal Motor Vehicle Safety Standards](https://www.govinfo.gov/content/pkg/CFR-2017-title49-vol6/xml/CFR-2017-title49-vol6-part571.xml). To meet these standards, vehicles must undergo an extensive, long-established testing process, regardless of whether the vehicle operates on gasoline or electricity. Separately, EV battery packs must meet their own testing standards. Moreover, EVs are designed with additional safety features that shut down the electrical system when they detect a collision or short circuit.

For more information, visit [DOE’s Alternative Fuel Data Center](https://afdc.energy.gov/vehicles/electric_maintenance.html).

* * *

1 U.S. Energy Information Administration (EIA): [Renewables became the second-most prevalent U.S. electricity source in 2020](https://www.eia.gov/todayinenergy/detail.php?id=48896). ↵

2 Electric vehicles (combined): [Where the Energy Goes: Electric Cars](https://www.fueleconomy.gov/feg/atv-ev.shtml). Gasoline vehicles (combined): [Where the Energy Goes: Gasoline Vehicles](https://www.fueleconomy.gov/feg/atv.shtml) ↵

3 Assumptions: EV with 300-mile range; vehicle lifetime of 173,151 miles for both EV and gas car; 30.7 MPG gas car; and U.S. average grid emissions.  ↵

4Recurrent, [New Study: How Long Do Electric Car Batteries Last?](https://www.recurrentauto.com/research/how-long-do-ev-batteries-last), Liz Najman, March 27, 2023.  ↵

5 Department of Energy (DOE), Federal Energy Management Program, [Bidirectional Charging and Electric Vehicles for Mobile Storage](https://www.energy.gov/eere/femp/bidirectional-charging-and-electric-vehicles-mobile-storage). ↵

6 U.S. Driving Research and Innovation for Vehicle Efficiency and Energy Sustainability (USDRIVE), [Summary Report on EVs at Scale and the U.S. Electric Power System (pdf)](https://www.energy.gov/sites/prod/files/2019/12/f69/GITT%20ISATT%20EVs%20at%20Scale%20Grid%20Summary%20Report%20FINAL%20Nov2019.pdf) (706 KB, November 2019); and DOE, [Electric Vehicles at Scale – Phase I Analysis: High EV Adoption Impacts on the Western U.S. Power Grid (pdf)](https://www.pnnl.gov/sites/default/files/media/file/EV-AT-SCALE_1_IMPACTS_final.pdf) (15.3 MB, July 2020).  ↵

7 Nature Energy, [Charging infrastructure access and operation to reduce the grid impacts of deep electric vehicle adoption](https://www.nature.com/articles/s41560-022-01105-7), September 22, 2022.  ↵

8 E & E News: Renewable Energy, [Why Electric Vehicles Won’t Break the Grid](https://www.scientificamerican.com/article/why-electric-vehicles-wont-break-the-grid/), September 19, 2022.  ↵

9 U.S. Energy Information Administration, [2020 Residential Energy Consumption Survey](https://www.eia.gov/consumption/residential/data/2020/index.php?view=consumption), Detailed end-use consumption and expenditure estimates, Tables [CE5.3a (pdf)](https://www.eia.gov/consumption/residential/data/2020/c&e/pdf/ce5.3a.pdf) (436 KB) & [CE5.3b (pdf)](https://www.eia.gov/consumption/residential/data/2020/c&e/pdf/ce5.5b.pdf) (371 KB) June 2023.  ↵

10 U.S. Department of Transportation, Federal Highway Administration, [NextGen Origin-Destination Data Products](https://nhts.ornl.gov/od/?utm_medium=email&utm_source=govdelivery), accessed June 28, 2024.  ↵

11 [AAA Electric Vehicle Range Testing Report (pdf)](https://www.aaa.com/AAA/common/AAR/files/AAA-Electric-Vehicle-Range-Testing-Report.pdf) (7.3 MB, February 2019) ↵

## [Green Vehicle Guide](/greenvehicles)

Open Sidenav Menu Close Sidenav Menu

  * [Learn About Green Vehicles](/greenvehicles/learn-about-green-vehicles)expand or collapse the child menu
    * [What is a Green Vehicle?](/greenvehicles/learn-about-green-vehicles)
    * [Consider a SmartWay Vehicle](/greenvehicles/consider-smartway-vehicle)
    * [EVs and Plug-In Hybrid EVs](/greenvehicles/electric-plug-hybrid-electric-vehicles)
    * [EV Charging - The Basics](/greenvehicles/plug-electric-vehicle-charging-basics)
    * [EV Charging – The Details](/greenvehicles/plug-electric-vehicle-charging-details)
    * [Setting up Home EV Charging](/greenvehicles/getting-started-home-ev-charging)
    * [Tips for EV Drivers](/greenvehicles/watts-important-seven-tips-every-ev-driver-should-know)
    * [EV Myths](/greenvehicles/electric-vehicle-myths)
    * [EV Testing](/greenvehicles/fuel-economy-and-ev-range-testing)
    * [Hydrogen in Transportation](/greenvehicles/hydrogen-transportation)
  * [Help Make Transportation Greener](/greenvehicles/help-make-transportation-greener)expand or collapse the child menu
    * [Compare Your Gas Car to an EV](/greenvehicles/comparison-your-car-vs-electric-vehicle)
    * [True Cost of Car Ownership](/greenvehicles/true-cost-car-ownership)
    * [Buy Green / Save Green](/greenvehicles/help-make-transportation-greener)
    * [We've Done Big Things. We Can Do Big Things.](/greenvehicles/we-can-do-big-things)
    * [Promoting Green Vehicles](/greenvehicles/promoting-green-vehicles)
    * [Advanced Gas and Diesel Vehicles](/greenvehicles/advanced-gasoline-and-diesel-vehicles)
  * [Transportation & Climate Change](/greenvehicles/why-we-need-decarbonize-transportation)expand or collapse the child menu
    * [Why We Need to Decarbonize Transportation](/greenvehicles/why-we-need-decarbonize-transportation)
    * [How We Get There – National Blueprint for Decarbonizing Transportation](/greenvehicles/us-national-blueprint-transportation-decarbonization "/node/280656")
    * [Next Steps / What You Can Do](/greenvehicles/national-blueprint-decarbonizing-transportation-what-comes-next)
  * [Vehicles, Greenhouse Gases & Smog](/greenvehicles/smog-vehicle-emissions)expand or collapse the child menu
    * [Smog Vehicle Emissions](/greenvehicles/smog-vehicle-emissions)
    * [GHG Emissions from a Typical Passenger Vehicle](/greenvehicles/greenhouse-gas-emissions-typical-passenger-vehicle)
    * [Fast Facts on Transportation GHG Emissions in the US](/greenvehicles/fast-facts-transportation-greenhouse-gas-emissions)
    * [Routes to a Lower GHG Transportation Future](/greenvehicles/routes-lower-greenhouse-gas-emissions-transportation-future)
    * [Automotive Trends Report](/automotive-trends)
    * [50 Years of Automotive Trends](/greenvehicles/50-years-epas-automotive-trends-report)
  * [Fuel Economy](/greenvehicles/learn-about-fuel-economy-label)expand or collapse the child menu
    * [Learn about the Fuel Economy Label](/greenvehicles/learn-about-fuel-economy-label)
    * [How MPG Affects Fuel Costs](/greenvehicles/miles-gallon-mpg-math)
    * [Your Mileage May Vary](/greenvehicles/your-mileage-may-vary)
    * [Testing at Our Lab](/greenvehicles/fuel-economy-and-ev-range-testing)
  * [Transportation Down the Road](/greenvehicles/what-if-ideas-reducing-transportation-greenhouse-gases)expand or collapse the child menu
    * [Self-Driving Vehicles](/greenvehicles/self-driving-vehicles)
    * [Shared Mobility](/greenvehicles/shared-mobility)
    * [What if: Ideas for Reducing Transportation GHG](/greenvehicles/what-if-ideas-reducing-transportation-greenhouse-gases)
  * [Find a SmartWay Vehicle](/greenvehicles/find-smartway-vehicle)
  * [Sign up for E-Updates](/greenvehicles/forms/green-vehicle-guide-e-updates)



[Contact Us About the Green Vehicle Guide](/greenvehicles/forms/contact-us-about-green-vehicle-guide)

[Contact Us](/greenvehicles/forms/contact-us-about-green-vehicle-guide) to ask a question, provide feedback, or report a problem.

Last updated on January 23, 2025

  * [Assistance](/lep/assistance)
  * [Ayuda](/lep/assistance#esp)
  * [Arabic](/lep/assistance#ar)
  * [Chinese (simplified)](/lep/assistance#chi-s)
  * [Chinese (traditional)](/lep/assistance#chi-tr)
  * [Aide](/lep/assistance#fr)
  * [Asistans](/lep/assistance#hc)
  * [Korean](/lep/assistance#kor)
  * [Assistência](/lep/assistance#port)
  * [Russian](/lep/assistance#rus)
  * [Tulong](/lep/assistance#tag)
  * [Vietnamese](/lep/assistance#viet)



![United States Environmental Protection Agency](/themes/epa_theme/images/epa-seal.svg)

## Discover.

  * [Accessibility Statement](/accessibility/epa-accessibility-statement)
  * [Budget & Performance](/planandbudget)
  * [Contracting](/contracts)
  * [EPA www Web Snapshot](/utilities/wwwepagov-snapshots)
  * [Grants](/grants)
  * [No FEAR Act Data](/ocr/no-fear-act-data)
  * [Plain Writing](/web-policies-and-procedures/plain-writing)
  * [Privacy](/privacy)
  * [Privacy and Security Notice](/privacy/privacy-and-security-notice)



## Connect.

  * [Data](/data)
  * [Inspector General](https://www.epaoig.gov/)
  * [Jobs](/careers)
  * [Newsroom](/newsroom)
  * [Regulations.gov](https://www.regulations.gov/)
  * [Subscribe](/newsroom/email-subscriptions-epa-news-releases)
  * [USA.gov](https://www.usa.gov/)
  * [White House](https://www.whitehouse.gov/)



## Ask.

  * [Contact EPA](/home/forms/contact-epa)
  * [EPA Disclaimers](/web-policies-and-procedures/epa-disclaimers)
  * [Hotlines](/aboutepa/epa-hotlines)
  * [FOIA Requests](/foia)
  * [Frequent Questions](/home/frequent-questions-specific-epa-programstopics)



## Follow.

  * [ ](https://www.facebook.com/EPA)
  * [ ](https://x.com/epa)
  * [ ](https://www.youtube.com/user/USEPAgov)
  * [ ](https://www.flickr.com/photos/usepagov)
  * [ ](https://www.instagram.com/epagov)


url: http://arxiv.org/abs/2012.04773v2
scrape_date: 2025-02-28T08:55:32.161454
content_type: markdown
hash: 473e6afacc51aedad12d246ab73b83ec729c4a5501c5f956ed713e2bac66bfcd
title:
[2012.04773v2] Effects of Electric Vehicle Adoption for State-Wide Intercity Trips on Emission Saving and Energy Consumption

content:
Skip to main content

[![Cornell University](/static/browse/0.3.4/images/icons/cu/cornell-reduced-white-SMALL.svg)](https://www.cornell.edu/)

We gratefully acknowledge support from the Simons Foundation, [member institutions](https://info.arxiv.org/about/ourmembers.html), and all contributors. [Donate](https://info.arxiv.org/about/donate.html)

[](/IgnoreMe)

[![arxiv logo](/static/browse/0.3.4/images/arxiv-logo-one-color-white.svg)](/) > [math](/list/math/recent) > arXiv:2012.04773v2 

[Help](https://info.arxiv.org/help) | [Advanced Search](https://arxiv.org/search/advanced)

All fields Title Author Abstract Comments Journal reference ACM classification MSC classification Report number arXiv identifier DOI ORCID arXiv author ID Help pages Full text

Search

[![arXiv logo](/static/browse/0.3.4/images/arxiv-logomark-small-white.svg)](https://arxiv.org/)

[ ![Cornell University Logo](/static/browse/0.3.4/images/icons/cu/cornell-reduced-white-SMALL.svg) ](https://www.cornell.edu/)

open search

GO

open navigation menu

## quick links

  * [Login](https://arxiv.org/login)
  * [Help Pages](https://info.arxiv.org/help)
  * [About](https://info.arxiv.org/about)



# Mathematics > Numerical Analysis

**arXiv:2012.04773v2** (math) 

[Submitted on 8 Dec 2020 ([v1](https://arxiv.org/abs/2012.04773v1)), last revised 24 May 2021 (this version, v2)]

# Title:Effects of Electric Vehicle Adoption for State-Wide Intercity Trips on Emission Saving and Energy Consumption

Authors:[Mohammadreza Kavianipour](https://arxiv.org/search/math?searchtype=author&query=Kavianipour,+M), [Hamid Mozafari](https://arxiv.org/search/math?searchtype=author&query=Mozafari,+H), [Mehrnaz Ghamami](https://arxiv.org/search/math?searchtype=author&query=Ghamami,+M), [Ali Zockaie](https://arxiv.org/search/math?searchtype=author&query=Zockaie,+A), [Robert Jackson](https://arxiv.org/search/math?searchtype=author&query=Jackson,+R)

View a PDF of the paper titled Effects of Electric Vehicle Adoption for State-Wide Intercity Trips on Emission Saving and Energy Consumption, by Mohammadreza Kavianipour and 4 other authors

[View PDF](/pdf/2012.04773v2)

> Abstract:Electric vehicles (EVs) are considered as sustainable alternatives to conventional vehicles, as they reduce emission and fossil fuel dependency. A recent study has proposed a charging infrastructure planning tool to support intercity trips for the estimated EV market share (6 percent) in Michigan for 2030. The main goal of this study is to estimate the emission reduction associated with this electrification rate and infrastructure investment for light duty vehicles. To this end, a state-of-the-art emission estimation framework is proposed to be applied to the state-wide intercity travels. The main contributions of the proposed framework includes: 1) Incorporating a micro emission estimation model for simulated vehicle trajectories of the intercity network of Michigan, 2) Adjusting the micro emission model results considering impacts of monthly travel demand and temperature variations, and heterogeneity of vehicles based on their make, model, and age. The emission estimation framework is then compared with the traditional VMT analysis method as a benchmark. Finally, five different scenarios are explored for EV adoption to assess potential emission savings from the given electrification rate for each scenario. The results suggest an annual CO2 emission savings of 0.58-0.92 million-ton. The CO2 social cost savings may justify the investment on the network electrification. Note that only 3.7 to 8.6 percent of the total EV energy requirements must be provided via the DC fast charger network proposed by the charging infrastructure planning tool. This requires annual energy consumption of 22.15 to 51.76 BWh for the estimated EV market share in Michigan for 2030. 

Comments: | 21 pages, 3 figures, Transportation Research Board 100th Annual Meeting  
---|---  
Subjects: |  Numerical Analysis (math.NA)  
Cite as: | [arXiv:2012.04773](https://arxiv.org/abs/2012.04773) [math.NA]  
  | (or  [arXiv:2012.04773v2](https://arxiv.org/abs/2012.04773v2) [math.NA] for this version)   
  |  <https://doi.org/10.48550/arXiv.2012.04773> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Mohammadreza Kavianipour [[view email](/show-email/04b3ec99/2012.04773)]   
**[[v1]](/abs/2012.04773v1)** Tue, 8 Dec 2020 22:39:22 UTC (533 KB)  
**[v2]** Mon, 24 May 2021 15:31:27 UTC (514 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Effects of Electric Vehicle Adoption for State-Wide Intercity Trips on Emission Saving and Energy Consumption, by Mohammadreza Kavianipour and 4 other authors

  * [View PDF](/pdf/2012.04773v2)
  * [Other Formats](/format/2012.04773v2)



[ ![license icon](https://arxiv.org/icons/licenses/by-4.0.png) view license ](http://creativecommons.org/licenses/by/4.0/ "Rights to this article")

Current browse context: 

math.NA

[< prev](/prevnext?id=2012.04773&function=prev&context=math.NA "previous in math.NA \(accesskey p\)")   |   [next >](/prevnext?id=2012.04773&function=next&context=math.NA "next in math.NA \(accesskey n\)")   


[new](/list/math.NA/new) |  [recent](/list/math.NA/recent) | [2020-12](/list/math.NA/2020-12)

Change to browse by: 

[cs](/abs/2012.04773?context=cs)  
[cs.NA](/abs/2012.04773?context=cs.NA)  
[math](/abs/2012.04773?context=math)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2012.04773)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2012.04773)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2012.04773)



[a](/static/browse/0.3.4/css/cite.css) export BibTeX citation Loading...

## BibTeX formatted citation

×

loading...

Data provided by: 

### Bookmark

[ ![BibSonomy logo](/static/browse/0.3.4/images/icons/social/bibsonomy.png) ](http://www.bibsonomy.org/BibtexHandler?requTask=upload&url=https://arxiv.org/abs/2012.04773&description=Effects of Electric Vehicle Adoption for State-Wide Intercity Trips on Emission Saving and Energy Consumption "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2012.04773&title=Effects of Electric Vehicle Adoption for State-Wide Intercity Trips on Emission Saving and Energy Consumption "Bookmark on Reddit")

Bibliographic Tools

# Bibliographic and Citation Tools

Bibliographic Explorer Toggle

Bibliographic Explorer _([What is the Explorer?](https://info.arxiv.org/labs/showcase.html#arxiv-bibliographic-explorer))_

Connected Papers Toggle

Connected Papers _([What is Connected Papers?](https://www.connectedpapers.com/about))_

Litmaps Toggle

Litmaps _([What is Litmaps?](https://www.litmaps.co/))_

scite.ai Toggle

scite Smart Citations _([What are Smart Citations?](https://www.scite.ai/))_

Code, Data, Media

# Code, Data and Media Associated with this Article

alphaXiv Toggle

alphaXiv _([What is alphaXiv?](https://alphaxiv.org/))_

Links to Code Toggle

CatalyzeX Code Finder for Papers _([What is CatalyzeX?](https://www.catalyzex.com))_

DagsHub Toggle

DagsHub _([What is DagsHub?](https://dagshub.com/))_

GotitPub Toggle

Gotit.pub _([What is GotitPub?](http://gotit.pub/faq))_

Huggingface Toggle

Hugging Face _([What is Huggingface?](https://huggingface.co/huggingface))_

Links to Code Toggle

Papers with Code _([What is Papers with Code?](https://paperswithcode.com/))_

ScienceCast Toggle

ScienceCast _([What is ScienceCast?](https://sciencecast.org/welcome))_

Demos

# Demos

Replicate Toggle

Replicate _([What is Replicate?](https://replicate.com/docs/arxiv/about))_

Spaces Toggle

Hugging Face Spaces _([What is Spaces?](https://huggingface.co/docs/hub/spaces))_

Spaces Toggle

TXYZ.AI _([What is TXYZ.AI?](https://txyz.ai))_

Related Papers

# Recommenders and Search Tools

Link to Influence Flower

Influence Flower _([What are Influence Flowers?](https://influencemap.cmlab.dev/))_

Core recommender toggle

CORE Recommender _([What is CORE?](https://core.ac.uk/services/recommender))_

  * Author
  * Venue
  * Institution
  * Topic



About arXivLabs 

# arXivLabs: experimental projects with community collaborators

arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website.

Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them.

Have an idea for a project that will add value for arXiv's community? [**Learn more about arXivLabs**](https://info.arxiv.org/labs/index.html).

[Which authors of this paper are endorsers?](/auth/show-endorsers/2012.04773) | [Disable MathJax](javascript:setMathjaxCookie\(\)) ([What is MathJax?](https://info.arxiv.org/help/mathjax.html)) 

  * [About](https://info.arxiv.org/about)
  * [Help](https://info.arxiv.org/help)



  * contact arXivClick here to contact arXiv [ Contact](https://info.arxiv.org/help/contact.html)
  * subscribe to arXiv mailingsClick here to subscribe [ Subscribe](https://info.arxiv.org/help/subscribe)



  * [Copyright](https://info.arxiv.org/help/license/index.html)
  * [Privacy Policy](https://info.arxiv.org/help/policies/privacy_policy.html)



  * [Web Accessibility Assistance](https://info.arxiv.org/help/web_accessibility.html)
  * [arXiv Operational Status ](https://status.arxiv.org)  
Get status notifications via [email](https://subscribe.sorryapp.com/24846f03/email/new) or [slack](https://subscribe.sorryapp.com/24846f03/slack/new)


url: http://arxiv.org/abs/2403.13373v1
title: [2403.13373v1] Charged Momentum: Electric Vehicle Surge in India's 2023 Landscape
scrape_date: 2025-02-28T08:55:32.192847
content_type: markdown
hash: e00d1639997f8ccb98a5a321d1e496704d236f907fbd0300b55102817c7fc24a
content:
Skip to main content

[![Cornell University](/static/browse/0.3.4/images/icons/cu/cornell-reduced-white-SMALL.svg)](https://www.cornell.edu/)

We gratefully acknowledge support from the Simons Foundation, [member institutions](https://info.arxiv.org/about/ourmembers.html), and all contributors. [Donate](https://info.arxiv.org/about/donate.html)

[](/IgnoreMe)

[![arxiv logo](/static/browse/0.3.4/images/arxiv-logo-one-color-white.svg)](/) > [eess](/list/eess/recent) > arXiv:2403.13373v1 

[Help](https://info.arxiv.org/help) | [Advanced Search](https://arxiv.org/search/advanced)

All fields Title Author Abstract Comments Journal reference ACM classification MSC classification Report number arXiv identifier DOI ORCID arXiv author ID Help pages Full text

Search

[![arXiv logo](/static/browse/0.3.4/images/arxiv-logomark-small-white.svg)](https://arxiv.org/)

[ ![Cornell University Logo](/static/browse/0.3.4/images/icons/cu/cornell-reduced-white-SMALL.svg) ](https://www.cornell.edu/)

open search

GO

open navigation menu

## quick links

  * [Login](https://arxiv.org/login)
  * [Help Pages](https://info.arxiv.org/help)
  * [About](https://info.arxiv.org/about)



# Electrical Engineering and Systems Science > Systems and Control

**arXiv:2403.13373v1** (eess) 

[Submitted on 20 Mar 2024]

# Title:Charged Momentum: Electric Vehicle Surge in India's 2023 Landscape

Authors:[Rahul Wagh](https://arxiv.org/search/eess?searchtype=author&query=Wagh,+R)

View a PDF of the paper titled Charged Momentum: Electric Vehicle Surge in India's 2023 Landscape, by Rahul Wagh

[View PDF](/pdf/2403.13373v1)

> Abstract:Electric vehicles (EVs) have emerged as a transformative force in India's transportation sector, offering a sustainable solution to the country's growing energy and environmental challenges. Against the backdrop of rapid urbanization, rising pollution levels, and the need for energy security, EVs have gained traction as a viable alternative to traditional internal combustion engine vehicles. This paper provides a comprehensive analysis of the electric vehicle market in India, focusing particularly on the landscape of 2023. It emphasizes key aspects such as the 2023 scenario of EV adoption, the role of indigenous manufacturers, dominant players shaping the market, and the influence of government policies and initiatives, including the FAME I and II schemes. Furthermore, the paper delves into EV sales data for the fiscal year 2023, offering insights into market trends and consumer preferences. By elucidating the current state of EVs in India, this paper aims to contribute to a deeper understanding of the country's transition towards sustainable mobility and its implications for energy, environment, and economy. 

Subjects: |  Systems and Control (eess.SY)  
---|---  
Cite as: | [arXiv:2403.13373](https://arxiv.org/abs/2403.13373) [eess.SY]  
  | (or  [arXiv:2403.13373v1](https://arxiv.org/abs/2403.13373v1) [eess.SY] for this version)   
  |  <https://doi.org/10.48550/arXiv.2403.13373> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Rahul Wagh [[view email](/show-email/75e86769/2403.13373)]   
**[v1]** Wed, 20 Mar 2024 08:09:11 UTC (1,037 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Charged Momentum: Electric Vehicle Surge in India's 2023 Landscape, by Rahul Wagh

  * [View PDF](/pdf/2403.13373v1)
  * [Other Formats](/format/2403.13373v1)



[ ![license icon](https://arxiv.org/icons/licenses/by-sa-4.0.png) view license ](http://creativecommons.org/licenses/by-sa/4.0/ "Rights to this article")

Current browse context: 

eess.SY

[< prev](/prevnext?id=2403.13373&function=prev&context=eess.SY "previous in eess.SY \(accesskey p\)")   |   [next >](/prevnext?id=2403.13373&function=next&context=eess.SY "next in eess.SY \(accesskey n\)")   


[new](/list/eess.SY/new) |  [recent](/list/eess.SY/recent) | [2024-03](/list/eess.SY/2024-03)

Change to browse by: 

[cs](/abs/2403.13373?context=cs)  
[cs.SY](/abs/2403.13373?context=cs.SY)  
[eess](/abs/2403.13373?context=eess)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2403.13373)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2403.13373)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2403.13373)



[a](/static/browse/0.3.4/css/cite.css) export BibTeX citation Loading...

## BibTeX formatted citation

×

loading...

Data provided by: 

### Bookmark

[ ![BibSonomy logo](/static/browse/0.3.4/images/icons/social/bibsonomy.png) ](http://www.bibsonomy.org/BibtexHandler?requTask=upload&url=https://arxiv.org/abs/2403.13373&description=Charged Momentum: Electric Vehicle Surge in India's 2023 Landscape "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2403.13373&title=Charged Momentum: Electric Vehicle Surge in India's 2023 Landscape "Bookmark on Reddit")

Bibliographic Tools

# Bibliographic and Citation Tools

Bibliographic Explorer Toggle

Bibliographic Explorer _([What is the Explorer?](https://info.arxiv.org/labs/showcase.html#arxiv-bibliographic-explorer))_

Connected Papers Toggle

Connected Papers _([What is Connected Papers?](https://www.connectedpapers.com/about))_

Litmaps Toggle

Litmaps _([What is Litmaps?](https://www.litmaps.co/))_

scite.ai Toggle

scite Smart Citations _([What are Smart Citations?](https://www.scite.ai/))_

Code, Data, Media

# Code, Data and Media Associated with this Article

alphaXiv Toggle

alphaXiv _([What is alphaXiv?](https://alphaxiv.org/))_

Links to Code Toggle

CatalyzeX Code Finder for Papers _([What is CatalyzeX?](https://www.catalyzex.com))_

DagsHub Toggle

DagsHub _([What is DagsHub?](https://dagshub.com/))_

GotitPub Toggle

Gotit.pub _([What is GotitPub?](http://gotit.pub/faq))_

Huggingface Toggle

Hugging Face _([What is Huggingface?](https://huggingface.co/huggingface))_

Links to Code Toggle

Papers with Code _([What is Papers with Code?](https://paperswithcode.com/))_

ScienceCast Toggle

ScienceCast _([What is ScienceCast?](https://sciencecast.org/welcome))_

Demos

# Demos

Replicate Toggle

Replicate _([What is Replicate?](https://replicate.com/docs/arxiv/about))_

Spaces Toggle

Hugging Face Spaces _([What is Spaces?](https://huggingface.co/docs/hub/spaces))_

Spaces Toggle

TXYZ.AI _([What is TXYZ.AI?](https://txyz.ai))_

Related Papers

# Recommenders and Search Tools

Link to Influence Flower

Influence Flower _([What are Influence Flowers?](https://influencemap.cmlab.dev/))_

Core recommender toggle

CORE Recommender _([What is CORE?](https://core.ac.uk/services/recommender))_

  * Author
  * Venue
  * Institution
  * Topic



About arXivLabs 

# arXivLabs: experimental projects with community collaborators

arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website.

Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them.

Have an idea for a project that will add value for arXiv's community? [**Learn more about arXivLabs**](https://info.arxiv.org/labs/index.html).

[Which authors of this paper are endorsers?](/auth/show-endorsers/2403.13373) | [Disable MathJax](javascript:setMathjaxCookie\(\)) ([What is MathJax?](https://info.arxiv.org/help/mathjax.html)) 

  * [About](https://info.arxiv.org/about)
  * [Help](https://info.arxiv.org/help)



  * contact arXivClick here to contact arXiv [ Contact](https://info.arxiv.org/help/contact.html)
  * subscribe to arXiv mailingsClick here to subscribe [ Subscribe](https://info.arxiv.org/help/subscribe)



  * [Copyright](https://info.arxiv.org/help/license/index.html)
  * [Privacy Policy](https://info.arxiv.org/help/policies/privacy_policy.html)



  * [Web Accessibility Assistance](https://info.arxiv.org/help/web_accessibility.html)
  * [arXiv Operational Status ](https://status.arxiv.org)  
Get status notifications via [email](https://subscribe.sorryapp.com/24846f03/email/new) or [slack](https://subscribe.sorryapp.com/24846f03/slack/new)


url: https://greenly.earth/en-us/blog/industries/electric-cars-are-they-really-ecological
title: Electric Cars: Are They Really Ecological?
scrape_date: 2025-02-28T08:55:32.601546
content_type: markdown
hash: 10c4ec92533f0274944cfe71d09a6fbb0277197a7f3e127d6a23d385f11c7de1
content:
[![ ](https://greenly.cdn.prismic.io/greenly/Z7FUIp7c43Q3f1EK_GR-1-.svg)](/en-us)[![ ](https://greenly.cdn.prismic.io/greenly/Z7FVSJ7c43Q3f1EL_LEAF-1-.svg)](/en-us/leaf-media)

The voice of impact

  *   *   * 


![ ](https://greenly.cdn.prismic.io/greenly/Zt_o7xoQrfVKl40b_file-search-02.svg)

ESG / CSR

[Carbon accounting](/en-us/blog/company-guide/carbon-accounting)

[CSRD](/en-us/blog/company-guide/csrd)

[Debriefs](/en-us/blog/company-guide/debriefs)

[ESG Initiatives](/en-us/blog/company-guide/esg-initiatives)

[Legislation & Standards](/en-us/blog/company-guide/legislation-standards)

[Net zero trajectory](/en-us/blog/company-guide/net-zero-trajectory)

[Offset](/en-us/blog/company-guide/offset)

[Sustainable Procurement](/en-us/blog/company-guide/sustainable-procurement)

![ ](https://greenly.cdn.prismic.io/greenly/Zt_o7hoQrfVKl40a_building-06.svg)

Industries

[Bank](/en-us/blog/industries/bank)

[Celebrations](/en-us/blog/industries/celebrations)

[Construction](/en-us/blog/industries/construction)

[Cosmetic](/en-us/blog/industries/cosmetic)

[Education](/en-us/blog/industries/education)

[Event](/en-us/blog/industries/event)

[Finance](/en-us/blog/industries/finance)

[Food](/en-us/blog/industries/food)

[Insurance](/en-us/blog/industries/insurance)

[Manufacturing](/en-us/blog/industries/manufacturing)

[Media](/en-us/blog/industries/media)

[Technology](/en-us/blog/industries/technology)

[Textile](/en-us/blog/industries/textile)

[Tourism](/en-us/blog/industries/tourism)

[Transport](/en-us/blog/industries/transport)

![ ](https://greenly.cdn.prismic.io/greenly/Zt_o9RoQrfVKl40d_globe-04.svg)

Ecology

[Global Warming](/en-us/blog/ecology-news/global-warming)

[Initiatives & Lifestyle](/en-us/blog/ecology-news/initiatives-lifestyle)

[IPCC](/en-us/blog/ecology-news/ipcc)

[Life and earth sciences](/en-us/blog/ecology-news/life-earth-sciences)

[Policy](/en-us/blog/ecology-news/policy)

US

[Newsletter](/en-us/newsletter)[Request a demo](/en-us/demo2)

US

  * ![ ](https://greenly.cdn.prismic.io/greenly/Zt_o7xoQrfVKl40b_file-search-02.svg)ESG / CSR
  * ![ ](https://greenly.cdn.prismic.io/greenly/Zt_o7hoQrfVKl40a_building-06.svg)Industries
  * ![ ](https://greenly.cdn.prismic.io/greenly/Zt_o9RoQrfVKl40d_globe-04.svg)Ecology




MEASURE

ACT

COMFORM

CSO Connect

![meeting room with orange chairs](https://images.prismic.io/greenly/ZuBZkRoQrfVKl7Jy_4.jpg?auto=format,compress)[Direct discussions with CSO Managers who share feedbacks and advices.](/en-us/leaf-media/cso-connect-interviews)

Greenlyhttps://www.greenly.earth/https://images.prismic.io/greenly/43d30a11-8d8a-4079-b197-b988548fad45_Logo+Greenly+x3.pngGreenly, la plateforme tout-en-un dédiée à toutes les entreprises désireuses de mesurer, piloter et réduire leurs émissions de CO2.Greenlyhttps://www.greenly.earth/Greenly, la plateforme tout-en-un dédiée à toutes les entreprises désireuses de mesurer, piloter et réduire leurs émissions de CO2.Descending4

Home

1

Blog

2

Category

3

Electric Cars: Are They Really Ecological?

4

[Media >](/en-us/leaf-media)[ All articles >](/en-us/blog)[ Transport > ](/en-us/blog/ecology-news/transport)Electric Cars: Are They Really Ecological?

# Electric Cars: Are They Really Ecological?

IndustriesTransport

Level

![Hero Image](https://images.prismic.io/greenly/4352e912-ce01-4e59-8be4-4fbe7f533dbd_train+v+car+article+image2.jpg?auto=format,compress)

![Kara Anderson](https://images.prismic.io/greenly/f9859071-2178-4b79-8ed7-3269e73cdd6e_Image-1+%281%29.jpg?auto=compress,format)

By

[Kara Anderson](/en-us/team/kara-anderson)

updated Jul 17, 2024

UK Copywriter at Greenly

![Hero Image](https://images.prismic.io/greenly/4352e912-ce01-4e59-8be4-4fbe7f533dbd_train+v+car+article+image2.jpg?auto=format,compress)

![Cars in the parking of Tesla](https://images.prismic.io/greenly/4352e912-ce01-4e59-8be4-4fbe7f533dbd_train+v+car+article+image2.jpg?auto=format,compress)

Electric cars are becoming mainstream, but does that mean they’re better for the environment? According to the experts, yes. Read our article to learn more.

Industries

2022-09-29T00:00:00.000Z

2024-07-17T00:00:00.000Z

en-us

Electric cars and electric [vehicles](https://greenly.earth/en-us/blog/ecology-news/vehicle-emissions-whats-the-impact-on-the-planet) (EVs)are designed to be an eco-friendly alternative to those that run on [fossil fuels](https://greenly.earth/en-us/blog/ecology-news/fossil-fuels-pros-cons-and-alternatives). This has led global leaders and car makers to embrace electric vehicles as part of their [carbon emission reduction](https://greenly.earth/en-us/blog/company-guide/decarbonization-meanings-technology-and-goals) strategies. 

General Motors, for example, has gone so far as to [announce](https://cnbc.com/2021/01/28/general-motors-plans-to-exclusively-offer-electric-vehicles-by-2035.html#:~:text=GM%20plans%20to%20exclusively%20offer,its%20global%20products%20and%20operations.) that it will only sell electric cars and light trucks by 2035 and that it will completely transform its manufacturing to battery-powered designs. Similarly, Volvo [plans](https://media.volvocars.com/global/en-gb/media/pressreleases/277409/volvo-cars-to-be-fully-electric-by-2030) to pivot to electric-only new car sales by 2030. 

Yet, no industry comes without an environmental footprint. 

Some people have raised legitimate concerns that mining rare earth minerals for electric car [batteries](https://greenly.earth/en-us/blog/ecology-news/the-harmful-effects-of-our-lithium-batteries) could put biodiverse regions at risk. Others have noted that we don't have a cost-effective means to [recycle electric](https://greenly.earth/en-us/blog/ecology-news/why-e-waste-is-becoming-an-issue) car batteries. 

Does this mean that electric cars are worse than regular cars? Experts say no, but they do have some important environmental pitfalls that need to be addressed. 

**👉 In this article, we examine the environmental impacts of electric cars, discuss strategies to mitigate these effects, and debunk common myths surrounding their use.**

Close

![Youtube cover picture](https://images.prismic.io/greenly/8b650048-5e90-449b-932e-5f5a22d6a035_maxresdefault+%2825%29+%281%29.jpg?auto=compress,format)

## What are electric cars?

“ Electric cars are vehicles powered by electric motors using energy stored in rechargeable batteries. Unlike traditional internal combustion engine vehicles that run on petrol or diesel, electric cars produce no exhaust emissions, contributing to reduced air pollution. They are recharged by plugging into an electrical outlet or charging station, and advancements in battery technology continue to improve their range and efficiency. ”

Just like your average automatic transmission car, an electric vehicle powers on with ignition, accelerates with the acceleration pedal, and stops with the brakes. The main difference between an EV and a fossil-fuel-powered car is the design of its motor.

Electric vehicles are powered by batteries which must be periodically re-charged using a charging station connected to an [electricity](https://greenly.earth/en-us/blog/company-guide/why-are-electricity-grids-a-challenge-for-the-us-transition) power source. This is familiar to most people because it's the same way we charge our phones, computers, and other electronic devices and appliances. 

Most electric vehicles use a lithium-ion battery with a relatively simple design. In fact, there are only [20](https://ennovi.com/resource-articles/electric-vehicle-drivetrains-only-have-20-moving-parts-compared-to-over-200-in-conventional-automobiles/#:~:text=The%20company%20says%20its%20drivetrain,tanks%2C%20valvetrains%20or%20exhaust%20systems.) moving parts in an EV motor versus almost 2,000 in the engine of a comparable internal combustion engine (ICE) vehicle.

![electric car on charge](https://images.prismic.io/greenly/41f01c88-466e-4154-ba91-56104a594e75_lithium+article+image+6.jpg?auto=format,compress)

### How do electric cars work? 

Electric cars, or EVs (Electric Vehicles), operate solely on electrical energy, eliminating the need for petrol or diesel. The fundamental components of an EV include the electric motor, battery pack, inverter, and various control systems. Here’s a detailed look at how they work:

  * **Electric motor** : The heart of an EV is its electric motor, which can be either an AC (Alternating Current) or DC (Direct Current) motor. The motor converts electrical energy from the battery into mechanical energy, driving the wheels. This process is highly efficient, with electric motors often achieving efficiency rates above [77%](https://www.fueleconomy.gov/feg/evtech.shtml#:~:text=Energy%20efficient.,to%20power%20at%20the%20wheels.). For comparison, conventional petrol vehicles only convert between 12% and 30% of the energy stored in the fuel into power! 
  * **Battery pack** : The energy source for the motor is a large battery pack, typically composed of numerous lithium-ion cells. These batteries store the electrical energy needed to power the vehicle. Modern EVs have battery management systems (BMS) to monitor and manage the performance, safety, and longevity of the battery pack.
  * **Inverter** : The inverter plays a crucial role by converting the DC power from the battery into AC power if the motor is an AC motor. It also manages the power flow during braking and other driving conditions to ensure optimal efficiency.
  * **Drivetrain** : Unlike internal combustion engine (ICE) vehicles that require a complex transmission system to manage power distribution and gear shifts, EVs tend to be much simpler. The motor is directly connected to the wheels via the drive shafts, allowing for smooth and instantaneous acceleration.
  * **Regenerative braking** : One of the innovative features of EVs is regenerative braking. When the driver applies the brakes, the electric motor reverses its function, acting as a generator. It converts the kinetic energy of the vehicle back into electrical energy, which is then fed back into the battery. This process not only helps in extending the range of the vehicle but also reduces wear on the braking system.
  * **Charging** : EVs are charged by connecting to an electrical power source through a charging port. There are various types of chargers, from slow home chargers (Level 1 and Level 2) to fast public chargers (Level 3 or DC fast chargers). The charging infrastructure is a critical aspect of EV usability and convenience.



Close

![youtube screenshot](https://images.prismic.io/greenly/65575db0531ac2845a254074_youtube.jpg?auto=format,compress)

  * Key differences between electric vehicles and fuel-powered vehicles:



**Quieter Operation** | Electric cars operate much more quietly, providing a smoother and more pleasant driving experience.  
---|---  
**Instant Torque and Faster Acceleration** | Electric motors provide instant torque, resulting in rapid acceleration without the need for gear shifts.  
**Maintenance** | Fewer moving parts in EVs mean lower maintenance requirements compared to gasoline vehicles, which have complex engines and transmission systems.  
**Energy Efficiency** | EVs are more energy-efficient, converting a higher percentage of energy from the battery to drive the wheels compared to the energy conversion in internal combustion engines.  
**Environmental Impact** | EVs produce no tailpipe emissions, significantly reducing their carbon footprint. However, the overall environmental impact depends on the source of electricity used to charge them.  
**Fueling Infrastructure** | Instead of refueling at gas stations, EVs require charging infrastructure, which is rapidly expanding but varies in availability.  
**Running Costs** | The cost per mile for driving an EV is generally lower than for gasoline vehicles due to cheaper electricity costs and lower maintenance expenses.  
  
## The different types of electric cars

There are four main types of vehicles that utilize some form of electric power, each offering different combinations of electric and fuel power:

#### Fully Electric Vehicle (EV)

  * **Power Source** : Fully powered by an electric motor.
  * **Charging** : Requires plugging into a charging station to recharge the battery.
  * **Operation** : Emits no tailpipe emissions, relying entirely on electricity for propulsion.
  * **Advantages:** EVs are ideal for urban environments due to their zero emissions and quiet operation. Advances in battery technology are extending their range and reducing charging times.  




#### Plug-in Hybrid Electric Vehicle (PHEV)

  * **Power Source** : Combines a combustion engine with an electric motor.
  * **Charging** : Needs to be plugged into a charging station to recharge the battery.
  * **Operation** : Can run on electric power alone for short distances, switching to the combustion engine for longer trips or when the battery is depleted.
  * **Advantages** : PHEVs offer the flexibility of electric driving for daily commutes with the backup of a combustion engine for longer journeys, making them a versatile option for varied driving needs.  




#### Hybrid Electric Vehicle (HEV)

  * **Power Source** : Integrates both a combustion engine and an electric motor.
  * **Charging** : The electric motor is recharged through regenerative braking and the combustion engine.
  * **Operation** : Uses the electric motor to assist the combustion engine, improving fuel efficiency and reducing emissions without requiring external charging.
  * **Advantages** : HEVs provide improved fuel efficiency and lower emissions compared to conventional petrol or diesel vehicles, making them an excellent choice for reducing environmental impact without changing driving habits significantly.  




#### Mild Hybrid Electric Vehicle (MHEV)

  * **Power Source** : Features a small electric motor paired with a combustion engine.
  * **Charging** : The electric motor is recharged by the engine and regenerative braking.
  * **Operation** : The electric motor cannot drive the vehicle independently but supports the combustion engine by reducing fuel consumption and assisting with acceleration.
  * **Advantages** : MHEVs enhance fuel efficiency and reduce emissions slightly, providing a cost-effective way to benefit from hybrid technology without the need for significant changes in driving or refueling practices.



![Electric cars charging](https://images.prismic.io/greenly/417170e7-ccbd-4092-8068-4e010c8d98c2_electric-car-2783573_1280+%281%29.jpg?auto=compress,format)

## What are hybrid vehicles? 

Hybrid vehicles offer a practical solution for reducing petrol costs and minimizing environmental impact, especially in areas lacking extensive charging infrastructure. 

Hybrid cars work by combining petroleum engines with electric motors to optimize fuel efficiency and reduce emissions. Depending on the design, they operate in several ways:

  * **Parallel hybrid** : Both the petrol engine and the electric motor can drive the car, either simultaneously or independently. At low speeds, the vehicle may rely solely on the electric motor, switching to the petrol engine at higher speeds or when additional power is needed.
  * **Series hybrid** : The petrol engine generates electricity to power the electric motor, which solely drives the wheels. This design effectively makes the petrol engine a generator for the electric system.
  * **Series-parallel hybrid** : A combination of both parallel and series designs, allowing for more flexible power management.



Hybrids are classified based on the power contribution of the electric motor:

  * **Strong hybrids** : The electric motor can drive the vehicle independently, providing significant power to reduce fuel consumption and emissions. 
  * **Mild hybrids** : The electric motor assists the petrol engine but cannot drive the car on its own. This system provides a boost during acceleration and enhances fuel efficiency.



Hybrid vehicles are popular for a number of reasons including: 

  * **Reduced CO2 emissions** : Hybrids emit less CO2 compared to conventional vehicles, contributing to a lower environmental footprint.
  * **Fuel efficiency** : By combining electric power with petrol, hybrids use less fuel, offering significant savings over time.
  * **Cost savings** : Lower fuel consumption translates to reduced operating costs, making hybrids economical in the long run.
  * **Regenerative braking** : This feature allows hybrids to recover and store energy during braking, improving efficiency.



### Technological Advancements

Recent advancements in hybrid technology include:

  * **Improved batteries** : Enhanced battery life and efficiency provide longer electric-only ranges.
  * **Smart energy management** : Advanced systems optimize the use of petrol and electric power for better performance and efficiency.
  * **Lightweight materials** : The use of lightweight materials improves overall vehicle efficiency and performance.



👉 Hybrid vehicles represent a bridge between conventional petrol vehicles and fully electric cars, providing a balance of performance, efficiency, and reduced environmental impact. However, since they still rely on the use of fossil fuels, hybrids will also need to be phased out in order to decarbonize the transport sector. 

![car exhaust ](https://images.prismic.io/greenly/87642711-7cfc-460d-a782-75dfcd2c93be_train+v+car+article+image7.jpg?auto=format,compress)

## What's the problem with cars? 

Cars and vehicles are a major environmental concern due to their impact on air quality and energy consumption. Traditional petrol and diesel engines emit pollutants like carbon monoxide and nitrogen oxides, which degrade the air we breathe and contribute to [health issues](https://greenly.earth/en-us/blog/ecology-news/how-global-warming-becomes-a-real-threat-for-our-health). Additionally, the high energy consumption from burning [fossil fuels](https://greenly.earth/en-gb/blog/ecology-news/fossil-fuels-pros-cons-and-alternatives) depletes non-renewable resources and increases greenhouse gas emissions.

These emissions are a significant driver of climate change, making it essential to reduce our reliance on fossil-fuel-powered vehicles to fight climate change. By shifting to electric vehicles and enhancing public transport, we can lower emissions and move toward a more sustainable future.

Close

![ ](https://images.prismic.io/greenly/Zpd8IR5LeNNTxOUh_youtube.jpg?auto=format,compress)

## Are electric cars sustainable?

Electric cars are often seen as a sustainable alternative to traditional cars, primarily because they do not emit exhaust emissions such as carbon dioxide (CO2), as no fuel is burned. However, they still require electricity to operate, and in the UK, a significant portion of electricity (about [40.8%](https://www.bbc.com/news/business-63976805)) is generated from burning fossil fuels.

US version: For now, a significant amount of electricity (about [60%](https://eia.gov/tools/faqs/faq.php?id=427&t=3)) still comes from fossil fuel sources in the US.

To fully assess the sustainability of electric cars, it is essential to compare the greenhouse gas emissions produced during electricity generation for charging the vehicle versus those emitted by driving an internal combustion engine car. This comparison varies depending on the energy mix of a region or country. For example, driving an electric car in Iceland would result in almost no emissions from both operation and charging due to the country's reliance on renewable energy sources like wind, solar, geothermal, and hydro.

In the US, however, the picture is more complicated as the situation differs by state. For example, the state of Maine sourced [72%](https://eia.gov/state/analysis.php?sid=ME#:~:text=19-,Renewable%20energy,of%20the%20state's%20renewable%20generation.) of its electricity from non-fossil fuel sources in 2021, while Texas relied on wind, solar, and nuclear for only [40%](https://vox.com/science-and-health/23577512/texas-clean-energy-wind-solar-natural-gas-ercot-blackout#:~:text=Clean%20energy%20is%20rapidly%20rising,in%20the%20state%20in%202022.) of its electricity. This means that driving an electric vehicle has a much lower environmental impact depending on where you live in the country. 

Yet despite these country and regional variations, according to the [European Energy Agency](https://eea.europa.eu/en), even when accounting for greenhouse gas emissions from electricity generation, electric cars generally have a smaller carbon footprint than petrol cars. EV emissions tend to be between [17 and 30%](https://edfenergy.com/energywise/electric-cars-and-environment#:~:text=Research%20by%20the%20European%20Energy,low%20carbon%20electricity%20is%20used.) lower than those of petrol or diesel cars.

👉 While the sustainability of electric cars depends on how the electricity they use is generated, they still represent a significant step towards reducing greenhouse gas emissions compared to traditional cars. As the energy grid becomes greener with more renewable sources such as wind and solar power, the carbon dioxide emissions associated with electric cars will continue to decrease, making them an increasingly sustainable option. Electric cars not only reduce direct emissions but also support the transition to renewable energy sources, contributing to a more sustainable future overall.

Close

![youtube screenshot](https://images.prismic.io/greenly/ZpeEcB5LeNNTxOZC_youtube.jpg?auto=format,compress)

## Is the manufacturing of electric cars ecological?

Another critical factor in electric car sustainability is their manufacturing practices. As with all vehicles, producing new electric vehicles requires raw materials. However, according to the [Union of Concerned Scientists](https://ucsusa.org/resources/driving-cleaner#:~:text=Manufacturing%20an%20EV%20results%20in,to%20produce%20an%20EV's%20battery.) (a non-profit science advocacy organization), the manufacturing of electric cars emits more carbon emissions than that of a petrol or diesel car. 

Unlike petrol-powered vehicles which use common metals and materials in their engines, most electric vehicles use rare earth elements such as lithium, nickel, cobalt, and graphite to manufacture the electric battery. Mining these elements requires carbon-intensive practices. 

Another concern is that mining these rare earth metals comes with environmental trade-offs. About [60%](https://theguardian.com/global-development/2019/dec/16/apple-and-google-named-in-us-lawsuit-over-congolese-child-cobalt-mining-deaths) of the reserves of cobalt are found in the Democratic Republic of Congo (DRC), where rainforests with rich biodiversity grow. Mining in these areas could threaten [biodiversity](https://greenly.earth/en-us/blog/ecology-news/what-does-biodiversity-loss-mean-for-humankind). 

It's estimated that half of the environmental impact of electric vehicles comes from producing their batteries. Addressing this issue involves improving battery technology, sourcing materials more sustainably, and increasing the use of recycled materials. As renewable energy becomes more prevalent in manufacturing processes, the overall environmental footprint of electric vehicle production is expected to decrease. Sustainable practices and advancements in technology are crucial for enhancing the overall sustainability of electric cars.

Close

![youtube screenshot](https://images.prismic.io/greenly/ZpeCAR5LeNNTxOX6_youtube.jpg?auto=format,compress)

Given that all raw materials extraction presents difficult trade-offs, it's also important to consider the alternative: many remaining oil reserves also exist in protected areas. 

For a direct comparison, however, the environmental impact of EVs improves over the lifetime of the vehicle compared to a conventional car. On average, the break-even point is reached after the EV has been driven between [17,500 and 21,300](https://blog.greenenergyconsumers.org/blog/lifecycle-emissions-of-electric-cars-vs.-gasoline#:~:text=Break%2DEven%20Point%20in%20Emissions&text=According%20to%20the%20graph%20below,points%20with%20their%20gas%20counterparts.) miles (this means the break-even point arrives after approximately 1.5 to 2 years of driving). And considering that most vehicles are driven 200,000 miles in their lifetime, EVs end up being considerably better for the environment over their total lifespan.

What's more, is that consumer reports suggest EV batteries could last around 17 years or 200,000 miles. The average lifespan of a conventional car is only around 12 years.

In sum, about 10-15 years of an EV's lifespan would operate with a better carbon footprint than conventional cars, assuming no change to manufacturing or battery technology. 

However, the end-of-life of batteries presents another ecological challenge...

## Can electric car batteries be recycled? 

Recycle rates of lead-acid batteries (ie. those found in traditional cars) are nearly 100% in developed nations. The US for example, [recycles](https://greenly.earth/en-us/blog/company-guide/recycling-all-you-need-to-know-on-plastic-management) around [99%](https://recyclingtoday.com/news/battery-council-international-lead-battery-recycling) of its lead-acid car batteries, and other developed nations boast similar stats. This makes the end-of-life disposal of traditional car batteries more ecological than is currently the case for EVs. 

Unfortunately, recycling lithium-ion batteries is a much less developed area. Lithium is found in such low traces within the batteries, that it is hard to recover. Globally, only [5%](https://cas.org/resources/cas-insights/sustainability/lithium-ion-battery-recycling#:~:text=Today%2C%20only%205%25%20of%20the,8%20million%20tons%20of%20waste.) of lithium in batteries is estimated to be recovered. 

As the market for EVs grows, more companies have shown interest in solving the problem of recycling batteries. Innovative companies are exploring solutions like mining them for their rare earth ingredients or repurposing them for renewable energy storage, helping to make electric cars greener. 

Recycling and reuse of outmoded EV car batteries is a promising field that would help offset the environmental impacts of manufacturing the batteries, by extending their useful lifespan.

Close

![youtube screenshot](https://images.prismic.io/greenly/65575db2531ac2845a254076_youtube.jpg?auto=format,compress)

## Electric car myths

**Myth:** Greenhouse gases released during the generation of electric power mean that electric cars are less environmentally friendly than conventional cars. 

**Fact:** It depends on the energy mix of your region. Compare the different estimated [greenhouse gas](https://greenly.earth/en-us/blog/company-guide/what-is-the-greenhouse-gas-protocol) (GHG) emissions from different car types, in the US you can use the “[Beyond Tailpipe Emissions Calculator](https://fueleconomy.gov/feg/Find.do?action=bt2)” available on the US EPA website. In the UK, similar information can be found through the UK Government's Vehicle Certification Agency [website](https://carfueldata.vehicle-certification-agency.gov.uk/search-new-or-used-cars.aspx).   


**Myth:** An EV battery runs out of charge too quickly to manage daily commutes and travel needs. 

**Fact:** The average driver in the US will travel around [37](https://kbb.com/car-advice/average-miles-driven-per-year#:~:text=The%20average%20miles%20driven%20per,to%20Department%20of%20Transportation%20statistics.) miles per day. In the UK this number is lower at [20](https://nimblefins.co.uk/cheap-car-insurance/average-car-mileage-uk#:~:text=Average%20Mileage%20per%20Day%2C%20Week,and%207%2C400%20miles%20a%20year.) miles per day. A fully charged EV can travel roughly 200 miles while charging at the station can deliver 100 miles of travel range. Therefore, for the average driver, electric vehicles should hold more than enough charge to cover daily commutes and travel needs. 

To understand an EV's range expectations, you'll need to check the specific car model specifications. 

Another factor impacting EV range is driver behavior and weather conditions. Cold temperatures can reduce driving range by up to 40%.  


**Myth:** Electric car models are very limited. 

**Fact:** A greater variety of electric cars is available. Manufacturers are developing them in a wide range of sizes, shapes, and hybrid vehicle options. Over 450 electric car models are available worldwide including Tesla's Cybertruck, which offers pick-up utility.

  
**Myth:** There aren't enough charging stations available. 

**Fact:** The US currently has over [160,000](https://electrek.co/2023/01/09/heres-how-many-ev-chargers-the-us-has-and-how-many-it-needs#:~:text=There%20are%20currently%20more%20than,need%20to%20install%20by%202030.) stations available and the UK has more than [45,000](https://zap-map.com/ev-stats/how-many-charging-points#:~:text=How%20many%20public%20charging%20points,charging%20devices%20since%20July%202022.), with more being installed daily. However, a little-known fact is they can even plug into standard 120 V (Level 1) outlets. The technology for charging plug-in vehicles is no different from charging your iPhone. 

However, most EV owners prefer 240 V charging systems, which can charge vehicles more quickly. Finally, a new generation of high-powered DC fast charging stations is also being built. 

The charging rates for each are as follows: 

  * 120V plug-in: slow
  * 240V plug-in: 10-20 miles of range per hour
  * Fast-charging station: 60 miles of range per 20 minutes  




**Myth:** The manufacturing process of electric batteries makes EVs worse for climate change than petrol-powered vehicles.

**Fact:** For new vehicles, this is true. However, the lifespan of an average vehicle is over ten years. [Lifetime emissions](https://greenly.earth/en-us/blog/company-guide/everything-you-need-to-know-about-lca-life-cycle-analysis-in-2022) for EVs are much lower. 

While the precise comparison depends on the car model and useful lifespan for each car type, charging emissions, and more. In general, a [300-mile](https://epa.gov/greenvehicles/electric-vehicle-myths#:~:text=comparable%20gasoline%20vehicles.-,Myth%20%231%3A%20Electric%20vehicles%20are%20worse%20for%20the%20climate%20than,EVs\)%20have%20no%20tailpipe%20emissions.) car range EV has roughly a third fewer emissions over its lifespan than a conventional car.   


**Myth:** Electric cars are dangerous to drive. 

**Fact:** All manufacturers are required to meet high safety standards. The standards between electric vehicles and conventional vehicles are no different in the US or UK. 

EV batteries also undergo intense testing to meet safety standards for avoiding short circuits from water or other factors. Car batteries are designed to detect risks and automatically shut down to avoid collisions and short-circuits. 

![Solar Charging Station in the Parking Lot](https://images.prismic.io/greenly/3b781885-4fb2-40a0-9142-2b4efe74d4e6_pexels-kindel-media-9800031+%281%29.jpg?auto=compress,format)

## How Greenly Can Help Companies 

Taking proactive steps in decarbonizing and adopting sustainable practices is crucial for long-term success. Greenly assists your company in embracing sustainability initiatives, ensuring you contribute positively to environmental stewardship.

**Comprehensive Carbon Management**

Greenly offers a range of services to help you effectively manage your carbon footprint:

  * **Measurement of GHG Emissions** : Track Scope 1, 2, and 3 emissions using advanced technology for an understanding of your greenhouse gas footprint.
  * **Custom Action Plans** : Develop tailored strategies with our climate experts, focusing on key areas for improvement and implementing effective changes.  




**Decarbonizing Your Supply Chain**

Greenly helps you engage suppliers and transition to low-carbon options, achieving greater transparency and effectively managing Scope 3 emissions. Our sustainable sourcing initiatives build greener partnerships and reduce emissions throughout your supply chain.  


**Intuitive and Seamless Platform**

Our user-friendly platform simplifies the process of calculating and monitoring your carbon footprint. With Greenly, your business can effortlessly manage its environmental impact, meet ESG goals, and enhance sustainability.  


👉 Greenly offers comprehensive support for your sustainability journey, from carbon measurement and custom action plans to supply chain decarbonization and seamless platform integration. With our help, your business can significantly reduce its environmental impact and achieve lasting sustainability.

[Contact Greenly today](https://greenly.earth/en-us) to start leading the way in sustainability and build a greener future for your company.

Summary

  * What are electric cars?
  * The different types of electric cars
  * What are hybrid vehicles? 
  * What's the problem with cars? 
  * Are electric cars sustainable?
  * Is the manufacturing of electric cars ecological?
  * Can electric car batteries be recycled? 
  * Electric car myths
  * How Greenly Can Help Companies 



Popular articles

[![EU flag](https://images.prismic.io/greenly/Zw6ERYF3NbkBXeC8_Templateimage.png?auto=format,compress)The Carbon Border Adjustment Mechanism (CBAM)](/en-us/blog/company-guide/the-carbon-border-adjustment-mechanism-cbam)[![Green leafs](https://images.prismic.io/greenly/89f6b0d9-0155-41d5-8b4f-9d2ebade2285_thumbnail.jpg?auto=format,compress)What is carbon management?](/en-us/blog/company-guide/what-is-carbon-management)[![man working at a desk](https://images.prismic.io/greenly/d99f9636-68ae-4d5b-9eb5-2c15eefdd569_ghg+changes+article+image+2.jpg?auto=compress,format)What are the 3 Pillars of Corporate Sustainability?](/en-us/blog/company-guide/what-are-the-3-pillars-of-corporate-sustainability)[![usd 20 dollar bills](https://images.prismic.io/greenly/Zy4fbK8jQArT0o9e_WhatistheSECandHowisitRelatedtotheEnvironment_.jpg?auto=format,compress)What is the SEC and How is it Related to the Environment?](/en-us/blog/industries/what-is-the-sec-and-how-is-it-related-to-the-environment)

Back to top of page

## More **articles**

[ View all](/en-us/blog)

![usd 20 dollar bills](https://images.prismic.io/greenly/Zy4fbK8jQArT0o9e_WhatistheSECandHowisitRelatedtotheEnvironment_.jpg?auto=format,compress)

Industries

Finance

1 min

## [What is the SEC and How is it Related to the Environment?](/en-us/blog/industries/what-is-the-sec-and-how-is-it-related-to-the-environment)

1 min

Level

How does the SEC, otherwise known as the U.S. Securities and Exchange Commission, help the United States regulate environmental policies?

![ ](https://greenly.cdn.prismic.io/greenly/Z7FVSJ7c43Q3f1EL_LEAF-1-.svg)

ESG / CSR

[Carbon accounting](/en-us/blog/company-guide/carbon-accounting)[CSRD](/en-us/blog/company-guide/csrd)[Debriefs](/en-us/blog/company-guide/debriefs)[ESG Initiatives](/en-us/blog/company-guide/esg-initiatives)[Legislation & Standards](/en-us/blog/company-guide/legislation-standards)[Net zero trajectory](/en-us/blog/company-guide/net-zero-trajectory)[Offset](/en-us/blog/company-guide/offset)[Sustainable Procurement](/en-us/blog/company-guide/sustainable-procurement)

Industries

[Bank](/en-us/blog/industries/bank)[Celebrations](/en-us/blog/industries/celebrations)[Construction](/en-us/blog/industries/construction)[Cosmetic](/en-us/blog/industries/cosmetic)[Education](/en-us/blog/industries/education)[Event](/en-us/blog/industries/event)[Finance](/en-us/blog/industries/finance)[Food](/en-us/blog/industries/food)[Insurance](/en-us/blog/industries/insurance)[Manufacturing](/en-us/blog/industries/manufacturing)[Media](/en-us/blog/industries/media)[Technology](/en-us/blog/industries/technology)[Textile](/en-us/blog/industries/textile)[Tourism](/en-us/blog/industries/tourism)[Transport](/en-us/blog/industries/transport)

Ecology

[Global Warming](/en-us/blog/ecology-news/global-warming)[Initiatives & Lifestyle](/en-us/blog/ecology-news/initiatives-lifestyle)[IPCC](/en-us/blog/ecology-news/ipcc)[Life and earth sciences](/en-us/blog/ecology-news/life-earth-sciences)[Policy](/en-us/blog/ecology-news/policy)

[![ ](https://greenly.cdn.prismic.io/greenly/Zt_n3xoQrfVKl4zj_Linkedin.svg)](https://www.linkedin.com/company/greenly-earth/)[![ ](https://greenly.cdn.prismic.io/greenly/Zt_n3hoQrfVKl4zi_Instagram.svg)](https://www.instagram.com/greenly.earth/?hl=en)


url: http://arxiv.org/abs/2404.01358v1
scrape_date: 2025-02-28T09:09:38.664326
content_type: markdown
hash: 8f1c7abea3676ccaee46c562aacdb8f0d11d8c268930b714a8d32ab6e3310a5d
title:
[2404.01358v1] Utilizing AI and Social Media Analytics to Discover Adverse Side Effects of GLP-1 Receptor Agonists

content:
Skip to main content

[![Cornell University](/static/browse/0.3.4/images/icons/cu/cornell-reduced-white-SMALL.svg)](https://www.cornell.edu/)

We gratefully acknowledge support from the Simons Foundation, [member institutions](https://info.arxiv.org/about/ourmembers.html), and all contributors. [Donate](https://info.arxiv.org/about/donate.html)

[](/IgnoreMe)

[![arxiv logo](/static/browse/0.3.4/images/arxiv-logo-one-color-white.svg)](/) > [q-bio](/list/q-bio/recent) > arXiv:2404.01358v1 

[Help](https://info.arxiv.org/help) | [Advanced Search](https://arxiv.org/search/advanced)

All fields Title Author Abstract Comments Journal reference ACM classification MSC classification Report number arXiv identifier DOI ORCID arXiv author ID Help pages Full text

Search

[![arXiv logo](/static/browse/0.3.4/images/arxiv-logomark-small-white.svg)](https://arxiv.org/)

[ ![Cornell University Logo](/static/browse/0.3.4/images/icons/cu/cornell-reduced-white-SMALL.svg) ](https://www.cornell.edu/)

open search

GO

open navigation menu

## quick links

  * [Login](https://arxiv.org/login)
  * [Help Pages](https://info.arxiv.org/help)
  * [About](https://info.arxiv.org/about)



# Quantitative Biology > Quantitative Methods

**arXiv:2404.01358v1** (q-bio) 

[Submitted on 1 Apr 2024]

# Title:Utilizing AI and Social Media Analytics to Discover Adverse Side Effects of GLP-1 Receptor Agonists

Authors:[Alon Bartal](https://arxiv.org/search/q-bio?searchtype=author&query=Bartal,+A), [Kathleen M. Jagodnik](https://arxiv.org/search/q-bio?searchtype=author&query=Jagodnik,+K+M), [Nava Pliskin](https://arxiv.org/search/q-bio?searchtype=author&query=Pliskin,+N), [Abraham Seidmann](https://arxiv.org/search/q-bio?searchtype=author&query=Seidmann,+A)

View a PDF of the paper titled Utilizing AI and Social Media Analytics to Discover Adverse Side Effects of GLP-1 Receptor Agonists, by Alon Bartal and 3 other authors

[View PDF](/pdf/2404.01358v1) [HTML (experimental)](https://arxiv.org/html/2404.01358v1)

> Abstract:Adverse side effects (ASEs) of drugs, revealed after FDA approval, pose a threat to patient safety. To promptly detect overlooked ASEs, we developed a digital health methodology capable of analyzing massive public data from social media, published clinical research, manufacturers' reports, and ChatGPT. We uncovered ASEs associated with the glucagon-like peptide 1 receptor agonists (GLP-1 RA), a market expected to grow exponentially to $133.5 billion USD by 2030. Using a Named Entity Recognition (NER) model, our method successfully detected 21 potential ASEs overlooked upon FDA approval, including irritability and numbness. Our data-analytic approach revolutionizes the detection of unreported ASEs associated with newly deployed drugs, leveraging cutting-edge AI-driven social media analytics. It can increase the safety of new drugs in the marketplace by unlocking the power of social media to support regulators and manufacturers in the rapid discovery of hidden ASE risks. 

Comments: | 19 pages, 7 figures, 3 tables, 1 Appendix table  
---|---  
Subjects: |  Quantitative Methods (q-bio.QM); Artificial Intelligence (cs.AI); Computation and Language (cs.CL); Information Retrieval (cs.IR); Machine Learning (cs.LG); Social and Information Networks (cs.SI)  
MSC classes: | 62  
Cite as: | [arXiv:2404.01358](https://arxiv.org/abs/2404.01358) [q-bio.QM]  
  | (or  [arXiv:2404.01358v1](https://arxiv.org/abs/2404.01358v1) [q-bio.QM] for this version)   
  |  <https://doi.org/10.48550/arXiv.2404.01358> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Alon Bartal [[view email](/show-email/5e7e952f/2404.01358)]   
**[v1]** Mon, 1 Apr 2024 09:48:14 UTC (1,229 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Utilizing AI and Social Media Analytics to Discover Adverse Side Effects of GLP-1 Receptor Agonists, by Alon Bartal and 3 other authors

  * [View PDF](/pdf/2404.01358v1)
  * [HTML (experimental)](https://arxiv.org/html/2404.01358v1)
  * [TeX Source](/src/2404.01358v1)
  * [Other Formats](/format/2404.01358v1)



[ ![license icon](https://arxiv.org/icons/licenses/by-nc-sa-4.0.png) view license ](http://creativecommons.org/licenses/by-nc-sa/4.0/ "Rights to this article")

Current browse context: 

q-bio.QM

[< prev](/prevnext?id=2404.01358&function=prev&context=q-bio.QM "previous in q-bio.QM \(accesskey p\)")   |   [next >](/prevnext?id=2404.01358&function=next&context=q-bio.QM "next in q-bio.QM \(accesskey n\)")   


[new](/list/q-bio.QM/new) |  [recent](/list/q-bio.QM/recent) | [2024-04](/list/q-bio.QM/2024-04)

Change to browse by: 

[cs](/abs/2404.01358?context=cs)  
[cs.AI](/abs/2404.01358?context=cs.AI)  
[cs.CL](/abs/2404.01358?context=cs.CL)  
[cs.IR](/abs/2404.01358?context=cs.IR)  
[cs.LG](/abs/2404.01358?context=cs.LG)  
[cs.SI](/abs/2404.01358?context=cs.SI)  
[q-bio](/abs/2404.01358?context=q-bio)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2404.01358)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2404.01358)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2404.01358)



[a](/static/browse/0.3.4/css/cite.css) export BibTeX citation Loading...

## BibTeX formatted citation

×

loading...

Data provided by: 

### Bookmark

[ ![BibSonomy logo](/static/browse/0.3.4/images/icons/social/bibsonomy.png) ](http://www.bibsonomy.org/BibtexHandler?requTask=upload&url=https://arxiv.org/abs/2404.01358&description=Utilizing AI and Social Media Analytics to Discover Adverse Side Effects of GLP-1 Receptor Agonists "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2404.01358&title=Utilizing AI and Social Media Analytics to Discover Adverse Side Effects of GLP-1 Receptor Agonists "Bookmark on Reddit")

Bibliographic Tools

# Bibliographic and Citation Tools

Bibliographic Explorer Toggle

Bibliographic Explorer _([What is the Explorer?](https://info.arxiv.org/labs/showcase.html#arxiv-bibliographic-explorer))_

Connected Papers Toggle

Connected Papers _([What is Connected Papers?](https://www.connectedpapers.com/about))_

Litmaps Toggle

Litmaps _([What is Litmaps?](https://www.litmaps.co/))_

scite.ai Toggle

scite Smart Citations _([What are Smart Citations?](https://www.scite.ai/))_

Code, Data, Media

# Code, Data and Media Associated with this Article

alphaXiv Toggle

alphaXiv _([What is alphaXiv?](https://alphaxiv.org/))_

Links to Code Toggle

CatalyzeX Code Finder for Papers _([What is CatalyzeX?](https://www.catalyzex.com))_

DagsHub Toggle

DagsHub _([What is DagsHub?](https://dagshub.com/))_

GotitPub Toggle

Gotit.pub _([What is GotitPub?](http://gotit.pub/faq))_

Huggingface Toggle

Hugging Face _([What is Huggingface?](https://huggingface.co/huggingface))_

Links to Code Toggle

Papers with Code _([What is Papers with Code?](https://paperswithcode.com/))_

ScienceCast Toggle

ScienceCast _([What is ScienceCast?](https://sciencecast.org/welcome))_

Demos

# Demos

Replicate Toggle

Replicate _([What is Replicate?](https://replicate.com/docs/arxiv/about))_

Spaces Toggle

Hugging Face Spaces _([What is Spaces?](https://huggingface.co/docs/hub/spaces))_

Spaces Toggle

TXYZ.AI _([What is TXYZ.AI?](https://txyz.ai))_

Related Papers

# Recommenders and Search Tools

Link to Influence Flower

Influence Flower _([What are Influence Flowers?](https://influencemap.cmlab.dev/))_

Core recommender toggle

CORE Recommender _([What is CORE?](https://core.ac.uk/services/recommender))_

  * Author
  * Venue
  * Institution
  * Topic



About arXivLabs 

# arXivLabs: experimental projects with community collaborators

arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website.

Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them.

Have an idea for a project that will add value for arXiv's community? [**Learn more about arXivLabs**](https://info.arxiv.org/labs/index.html).

[Which authors of this paper are endorsers?](/auth/show-endorsers/2404.01358) | [Disable MathJax](javascript:setMathjaxCookie\(\)) ([What is MathJax?](https://info.arxiv.org/help/mathjax.html)) 

  * [About](https://info.arxiv.org/about)
  * [Help](https://info.arxiv.org/help)



  * contact arXivClick here to contact arXiv [ Contact](https://info.arxiv.org/help/contact.html)
  * subscribe to arXiv mailingsClick here to subscribe [ Subscribe](https://info.arxiv.org/help/subscribe)



  * [Copyright](https://info.arxiv.org/help/license/index.html)
  * [Privacy Policy](https://info.arxiv.org/help/policies/privacy_policy.html)



  * [Web Accessibility Assistance](https://info.arxiv.org/help/web_accessibility.html)
  * [arXiv Operational Status ](https://status.arxiv.org)  
Get status notifications via [email](https://subscribe.sorryapp.com/24846f03/email/new) or [slack](https://subscribe.sorryapp.com/24846f03/slack/new)



  *[MSC]: Mathematical Subject Classification


url: https://pmc.ncbi.nlm.nih.gov/articles/PMC2905310/
scrape_date: 2025-02-28T09:09:38.805682
content_type: markdown
hash: 7ad9d5ab95fc856769f94dd9f4d37be75108317b7cfdeef8a0e5a86f85d9bd38
title:
            Can the use of creatine supplementation attenuate muscle loss in cachexia and wasting? - PMC
        

content:
Skip to main content 

![](/static/img/us_flag.svg)

An official website of the United States government 

Here's how you know

Here's how you know

![](/static/img/icon-dot-gov.svg)

**Official websites use .gov**   
A **.gov** website belongs to an official government organization in the United States. 

![](/static/img/icon-https.svg)

**Secure .gov websites use HTTPS**   
A **lock** (  Lock Locked padlock icon  ) or **https://** means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. 

[ ![
                                  NCBI home page
                              ](/static/img/ncbi-logos/nih-nlm-ncbi--white.svg) ](https://www.ncbi.nlm.nih.gov/)

Search 

Log in

  * [ Dashboard ](https://www.ncbi.nlm.nih.gov/myncbi/)
  * [ Publications ](https://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/)
  * [ Account settings ](https://www.ncbi.nlm.nih.gov/account/settings/)
  * Log out 



Search…  Search NCBI 

Primary site navigation 


Logged in as: ****

  * [ Dashboard ](https://www.ncbi.nlm.nih.gov/myncbi/)
  * [ Publications ](https://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/)
  * [ Account settings ](https://www.ncbi.nlm.nih.gov/account/settings/)



Log in 

[](/ "Home")

Search PMC Full-Text Archive Search in PMC ![Search](/static/img/usa-icons-bg/search--white.svg)

  * [ Advanced Search ](https://www.ncbi.nlm.nih.gov/pmc/advanced/)
  * [ Journal List ](/journals/)
  * [ User Guide ](/about/userguide/)



  *   * [ ](https://doi.org/10.1097/MCO.0b013e328331de63 "View on publisher site")
  * [ ](pdf/nihms202834.pdf "Download PDF")
  *   *   * ## PERMALINK

Copy




As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health.  
Learn more: [PMC Disclaimer](/about/disclaimer/) | [ PMC Copyright Notice ](/about/copyright/)

![NIHPA Author Manuscripts logo](https://cdn.ncbi.nlm.nih.gov/pmc/banners/logo-nihpa.png)

Curr Opin Clin Nutr Metab Care

. Author manuscript; available in PMC: 2010 Nov 1.

_Published in final edited form as:_ Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):623–627. doi: [10.1097/MCO.0b013e328331de63](https://doi.org/10.1097/MCO.0b013e328331de63)

  * [Search in PMC](https://www.ncbi.nlm.nih.gov/pmc/?term=%22Curr%20Opin%20Clin%20Nutr%20Metab%20Care%22%5Bjour%5D)
  * [Search in PubMed](https://pubmed.ncbi.nlm.nih.gov/?term=%22Curr%20Opin%20Clin%20Nutr%20Metab%20Care%22%5Bjour%5D)
  * [View in NLM Catalog](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Curr%20Opin%20Clin%20Nutr%20Metab%20Care%22%5BTitle%20Abbreviation%5D)
  * [Add to search](?term=%22Curr%20Opin%20Clin%20Nutr%20Metab%20Care%22%5Bjour%5D)



# Can the use of creatine supplementation attenuate muscle loss in cachexia and wasting?

[Giorgos K Sakkas](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sakkas%20GK%22%5BAuthor%5D)

### Giorgos K Sakkas

1Department of Medicine, University of Thessaly, Greece

2Center for Research and Technology, Thessaly, Greece

Find articles by [Giorgos K Sakkas](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sakkas%20GK%22%5BAuthor%5D)

1,2, [Morris Schambelan](https://pubmed.ncbi.nlm.nih.gov/?term=%22Schambelan%20M%22%5BAuthor%5D)

### Morris Schambelan

3Department of Medicine, University of California, San Francisco, CA, USA

4Division of Endocrinology, San Francisco General Hospital, San Francisco, CA, USA

Find articles by [Morris Schambelan](https://pubmed.ncbi.nlm.nih.gov/?term=%22Schambelan%20M%22%5BAuthor%5D)

3,4, [Kathleen Mulligan](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mulligan%20K%22%5BAuthor%5D)

### Kathleen Mulligan

3Department of Medicine, University of California, San Francisco, CA, USA

4Division of Endocrinology, San Francisco General Hospital, San Francisco, CA, USA

Find articles by [Kathleen Mulligan](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mulligan%20K%22%5BAuthor%5D)

3,4

  * Author information
  * Copyright and License information



1Department of Medicine, University of Thessaly, Greece

2Center for Research and Technology, Thessaly, Greece

3Department of Medicine, University of California, San Francisco, CA, USA

4Division of Endocrinology, San Francisco General Hospital, San Francisco, CA, USA

✉

Corresponding Author: Kathleen Mulligan, PhD, Department of Medicine, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, Bldg 30, Room 3501-K, San Francisco, CA 94110, USA, kathleen.mulligan@ucsf.edu, Phone: (415) 206-5882

[PMC Copyright notice](/about/copyright/)

PMCID: PMC2905310 NIHMSID: NIHMS202834 PMID: [19741514](https://pubmed.ncbi.nlm.nih.gov/19741514/)

The publisher's version of this article is available at [Curr Opin Clin Nutr Metab Care](https://doi.org/10.1097/MCO.0b013e328331de63)

## Abstract

### Purpose of review

Weight loss and low BMI due to an underlying illness have been associated with increased mortality, reduced functional capacity, and diminished quality of life. There is a need for safe, long- term approaches to maintain body weight in patients with cachexia or wasting. The purpose of this review is to highlight the scientific and clinical evidence derived from the recent literature investigating the rationale for and potential medical use of creatine supplementation in patients with cachexia or wasting.

### Recent findings

Some studies have demonstrated that supplementation with creatine can increase creatine reserves in skeletal muscle and increase muscle mass and performance in various disease states that affect muscle size and function. The mechanisms underlying these effects are not clear. It has been suggested that creatine supplementation may increase intramuscular phosphocreatine stores and promote more rapid recovery of adenosine triphosphate levels following exercise, thus allowing users to exercise for longer periods or at higher intensity levels. Other hypothesized mechanisms include attenuation of proinflammatory cytokines, stimulation of satellite cell proliferation, and up-regulation of genes that promote protein synthesis and cell repair.

### Summary

Creatine is a generally safe, low cost, over-the-counter nutritional supplement that shows potential in improving lean body mass and functionality in patients with wasting diseases. However, placebo-controlled studies have shown variable effects, with improvements in some and not in others. Additional studies with longer follow-up are required to identify the populations that might benefit most from creatine supplementation.

**Keywords:** lean body mass, muscle mass, energy metabolism, creatine

## Introduction

According to a recent consensus conference, cachexia “is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass” [1]. The reductions of skeletal muscle mass and fat mass occur in the context of severe weight loss [2**]. Weight loss and/or abnormally low BMI have been associated with increased mortality, reduced functional capacity and diminished quality of life [3]. More importantly, apart from the overall reduction in body mass, skeletal muscle atrophy, occurring as a result of either increased protein degradation or diminished protein synthesis, not only affects overall metabolism and mobility but, if untreated, can lead to death due to respiratory and cardiac muscle failure [4]. Treatments that reverse or forestall muscle loss could provide a potential target for the therapeutic approach to this syndrome.

A variety of non-pharmacological approaches to the treatment of muscle wasting have been investigated. Supplementation with creatine has been shown to improve muscle strength and delay fatigue, increase fat-free mass and enhance mitochondrial energy metabolism [5**]. The aim this review is to highlight the scientific and clinical evidence derived from the recent literature investigating the rationale and potential therapeutic role of creatine supplementation in patients with cachexia or wasting.

## Skeletal muscle loss in cachexia

Skeletal muscle protein breakdown occurs when the balance between protein synthesis and degradation is impaired. The preponderance of evidence supports the notion that muscle mass in wasting diseases is regulated primarily by protein synthesis, while changes in the rate of protein degradation are likely secondary [6]. However, studies using experimental models of cachexia suggest that both synthesis and degradation processes are involved simultaneously in cachectic conditions [2**]. Independent of the metabolic pathway, the resultant loss of skeletal muscle mass is related to diminished quality of life, severe fatigue, and reduced physical and functional capacity, factors that may reduce life expectancy [2**].

## Therapeutic use of creatine supplementation in cachexia

Creatine is a nutritional supplement that can be purchased over the counter and has been shown to increase energy availability during intense exercise, improve recovery after muscle fatigue, and increase muscle strength and size as well as total body weight and lean body mass [7, 8]. Daily oral supplementation of creatine can substantially increase the creatine reserves of human skeletal muscles [9].

Furthermore, there is also evidence that creatine supplementation has a therapeutic role in various disease states that affect muscle size and functionality through the enhancement of gene expression involved in hypertrophy [10] or the attenuation of the degenerative phase in certain myopathies [11]. Many neuromuscular and neurometabolic disorders are characterized by low intramuscular phosphocreatine levels, which contribute to increased fatigability and low functionality, factors well known to increase mortality [12]. Since these disorders share quite common pathways of cellular dysfunction, it has been hypothesized that the supplementation of creatine may favorably influence functionality and may improve quality of life. Studies in patients with various catabolic illnesses as well as in animal models have shown evidence of enhanced mitochondrial function and improved exercise performance following creatine supplementation [12]. However these findings cannot be generalized to all catabolic diseases. For example, in HIV-infected patients, creatine supplementation failed to enhance the benefits derived from three months of resistance exercise training [8*].

Discrepancies in the literature are also seen in studies with healthy volunteers. Studies of short-term (5-30 days) and chronic use (up to 12 months) of creatine supplementation have shown increases in total body weight [13, 14], muscle size [15], muscle strength and power output [16, 17] as well as intramuscular PCr levels (assessed by both 31P-MRS [18] and biopsy [19]), while other studies have failed to demonstrate positive effects on these same parameters [20-23]. The purported beneficial effect of creatine supplementation in patients with chronic diseases has been similarly challenged, with some studies showing positive effects [24-30] and others showing no benefit [31-35] (Table 1). It is not clear yet whether exercise training is needed in order to optimize the effect of creatine. However, preliminary data suggested that subjects who received both creatine and exercise training had amplified benefits compared to those who received exercise or creatine alone [37].

### Table 1.

Summary of randomized clinical trials investigating the effect of creatine supplementation in conditions that are associated with cachexia, muscle wasting, or functional impairment.

Author, year [reference number] | Population (N) | Study Design | Duration of Supplementation | Effects of Creatine  
---|---|---|---|---  
Gordon, 1995 [26] | Chronic heart failure (N=17) | RCT | 7 days | ↑Strength  
↑Endurance  
Tarnopolsky, 1997 [25] | Mitochondrial cytopathy (N=7) | RCT, crossover | 21 days | ↑MVC, ↑Exercise output, ↓Fatigue  
Vorgerd, 2000 [30] | McArdle disease (N=9) | RCT, crossover | 5 wks | ↑ Exercise tolerance  
↑ PCr depletion during exercise  
Walter, 2000 [28] | Muscular dystrophies (N=36) | RCT, crossover | 8 wks | ↑MVC, ↑ Physical activity  
Hespel, 2001 [15] | Disuse atrophy model (N=22) | RCT | 10 wks + rehab exercise | ↑Muscle CSA, ↑Exercise output, ↓Fatigue  
Walter, 2002 [33] | Myotonic dystrophy (N=34) | RCT | 8 wks | ↔ Muscle strength  
Vorgerd, 2002 [34] | McArdle disease (N=19) | RCT, crossover | 5 wks | ↓ Exercise tolerance with high-dose creatine  
Tarnopolsky, 2004 [31] | Myotonic muscular dystrophy type 1 (N=34) | RCT, crossover | 36 wks | ↔ LBM, ↔MVC, ↔Physical activity  
Tarnopolsky, 2004 [27] | Children with Duchenne muscular dystrophy (N=30) | RCT, crossover | 4 mos | ↑ Grip strength↑ LBM  
Tarnopolsky, 2007 [29] | Adults >65 years (N=39) | RCT | 6 mos + linoleic acid & resistance exercise | ↑ LBM↑ Muscle endurance↔ Strength, ↔ Physical function  
Johnston, 2009 [36] | Disuse atrophy model (N=7) | Randomized, single blind, crossover | 3 wks | ↑ LBM, ↑MVC, Exercise output  
Sakkas, 2009 [8] | HIV+ men (N=40) | RCT | 14 wks + resistance exercise | ↑ BW, ↑LBM, ↔MVC↔PCr recovery  
  
[Open in a new tab](table/T1/)

Abbreviations: RCT, randomized, double-blind, placebo-controlled clinical trial; CSA, cross sectional area; MVC, Maximum voluntary contraction; LBM, lean body mass; BW, body weight; PCr, phosphocreatine

## Creatine effect on muscle growth

Recent evidence sheds some light on the purported growth-promoting effects of creatine in skeletal muscle. Olsen et al. [37] reported that in healthy humans creatine supplementation in combination with strength training amplified the increase in satellite cell number and myonuclei concentration in skeletal muscle fibers, thus facilitating muscle growth and hypertrophy [37]. Creatine has also been reported to enhance expression of myogenin and other myogenic regulatory factors that regulate myosin heavy chain expression, affecting thus the contractile protein content (actin and myosin) [38]. It has been speculated that the potential growth-promoting effect that creatine exerts on skeletal muscle could be very useful in situations in which anabolic activity is suppressed, such as wasting diseases [39]. Further evidence of a growth-promoting effect of creatine supplementation was provided in a recent human study in which creatine supplementation significantly upregulated the mRNA content of genes and proteins involved in protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival; and reduced whole-body protein breakdown and leucine oxidation in humans [10]. The mechanism of action is still not clear. However, it has been suggested that water retention in muscle fibers caused by the osmotic potential of high intracellular creatine abundance [40] may be a major anabolic proliferative signal.

## Creatine supplementation in patients with muscle wasting and disuse

In muscle wasting, the preservation of the existing skeletal muscle mass is as important as attempts to return muscle mass to normal levels. Studies in rodents with steroid-induced myopathy have shown that creatine supplementation can reduce muscle loss, stabilize body weight, and preserve maximum oxygen consumption levels within normal range, thus exerting prophylactic effects compared to the animals with no creatine supplementation [41]. In research using disuse atrophy models, creatine supplementation for short periods attenuated skeletal muscle loss and preserved strength in the immobilized limbs [36*]. Creatine is taken up by both fast- and slow-twitch fibers, but fast-twitch fibers have a greater capacity for creatine storage than slow-twitch [42]. This difference could be very important for preservation of muscle fiber size since, in cachectic conditions, the fast-twitch fibers are lost more rapidly than slow twitch fibers, possibly due to an increase in protein oxidation and degradation [43] coupled with hypokinesis. So far, human studies have not yet demonstrated dramatic increases in skeletal muscle mass as a result of creatine supplementation, but no studies that have been conducted in cachectic patients were designed to directly address such a question. Still, Kley et al. [11] performed an excellent meta-analysis with the primary aim to determine the efficacy of creatine supplementation in various types of muscle disorders. The authors concluded from twelve trials with 266 patients that creatine supplementation in patients with muscular dystrophies significantly increased maximum voluntary contraction and lean body mass during creatine treatment compared to placebo [11]. However, they observed no improvements in patients with metabolic myopathies. Creatine supplementation showed only a moderate improvement in ATP consumption and PCr levels in patients with metabolic myopathies, possibly due to a defect in muscle creatine uptake [5**].

## Potential Ancillary Effect of Creatine Supplementation

It has been suggested by some investigators that cachexia is a condition of excess cytokine production that causes muscle loss, insulin resistance and oxidative stress [44]. Recent evidence suggests that creatine supplementation may attenuate the increase in plasma levels of the proinflammatory cytokines [45] and, in conjunction with aerobic exercise, while producing a greater improvement of glucose tolerance in humans [46*] and a protective effect on preventing immobilization induced decrease in muscle GLUT4 protein content, compared with aerobic exercise alone [47]. It has also been suggested that creatine supplementation could work as an appetite stimulant, since from studies in animal models, it has been found that creatine concentration in the brain plays a role in food intake regulation and body weight [48]. The mechanisms behind the observed anti-inflammatory and/or glucose sensitizing effect of creatine are not understood. However, further research is needed to clarify whether these improvements are due to a systemic or local effect of creatine, on leukocytes and skeletal muscles.

## Safety of creatine supplementation

When creatine is used according to the international guidelines for dosage and duration of supplementation [49] it is generally considered to be safe. Early reports of impairment of renal function were prompted by reports of elevated creatine kinase levels in the blood following a period of high dosage supplementation [50]. Similarly, supplementation with higher-than-recommended doses of creatine was associated with worsening exercise intolerance in patients with McArdle disease [34]. Based on a comprehensive review of the literature, it does not appear that creatine supplementation impairs renal function if it is taken according to recommended dosage regimens. However, long-term safety data on creatine supplementation are still not available [42]. Certainly, creatine supplementation should not be considered in patients with renal disease, and creatine kinase levels should be monitored during supplementation.

## Conclusion

Creatine supplementation has been suggested as a prophylactic or therapeutic agent in wasting diseases that affect muscle size and function. However, placebo-controlled studies have shown variable effects, with improvements in some and none in others. Additional studies with longer follow-up are required to identify the populations that might benefit most from creatine supplementation.

## Acknowledgments

**Funding:** This work was supported in part with support from the National Institutes of Health (AT00491, DK45833, DK54615, RR-00083).

The authors have declared that there is no conflict of interest. We acknowledge Dr. Christina Karatzaferi for critically reviewing the manuscript. This work was supported in part with support from the National Institutes of Health (AT00491, DK45833, DK54615, RR-00083).

## Footnotes

**Disclosure** : The authors have declared that there is no conflict of interest.

**Publisher's Disclaimer:** This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

## References

Papers of particular interest, published within the annual period of review, have been highlighted as:

* of special interest, ** of outstanding interest.

  * 1.Evans WJ, Morley JE, Argiles J, et al. Cachexia: a new definition. Clin Nutr. 2008;27(6):793–799. doi: 10.1016/j.clnu.2008.06.013. [[DOI](https://doi.org/10.1016/j.clnu.2008.06.013)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18718696/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Clin%20Nutr&title=Cachexia:%20a%20new%20definition&author=WJ%20Evans&author=JE%20Morley&author=J%20Argiles&volume=27&issue=6&publication_year=2008&pages=793-799&pmid=18718696&doi=10.1016/j.clnu.2008.06.013&)]
  * 2**.Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev. 2009;89(2):381–410. doi: 10.1152/physrev.00016.2008. [[DOI](https://doi.org/10.1152/physrev.00016.2008)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19342610/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Physiol%20Rev&title=Mechanisms%20of%20cancer%20cachexia&author=MJ%20Tisdale&volume=89&issue=2&publication_year=2009&pages=381-410&pmid=19342610&doi=10.1152/physrev.00016.2008&)]; This is an excellent review of the mechanisms of loss of both adipose tissue and skeletal muscle in cancer cachexia and in wasting diseases, also providing the first insights on how this evidence could be translated into clinical therapy
  * 3.Morley JE, Thomas DR. Cachexia: new advances in the management of wasting diseases. J Am Med Dir Assoc. 2008;9(4):205–210. doi: 10.1016/j.jamda.2008.02.006. [[DOI](https://doi.org/10.1016/j.jamda.2008.02.006)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18457793/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Am%20Med%20Dir%20Assoc&title=Cachexia:%20new%20advances%20in%20the%20management%20of%20wasting%20diseases&author=JE%20Morley&author=DR%20Thomas&volume=9&issue=4&publication_year=2008&pages=205-210&pmid=18457793&doi=10.1016/j.jamda.2008.02.006&)]
  * 4.Pajak B, Orzechowska S, Pijet B, et al. Crossroads of cytokine signaling--the chase to stop muscle cachexia. J Physiol Pharmacol. 2008;59(Suppl 9):251–264. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19261984/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Physiol%20Pharmacol&title=Crossroads%20of%20cytokine%20signaling--the%20chase%20to%20stop%20muscle%20cachexia&author=B%20Pajak&author=S%20Orzechowska&author=B%20Pijet&volume=59&issue=Suppl%209&publication_year=2008&pages=251-264&pmid=19261984&)]
  * 5**.Gualano B, Artioli GG, Poortmans JR, Lancha Junior AH. Exploring the therapeutic role of creatine supplementation. Amino Acids. 2009 doi: 10.1007/s00726-009-0263-6. Mar 1 – Epub ahead of print. [[DOI](https://doi.org/10.1007/s00726-009-0263-6)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19253023/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Amino%20Acids&title=Exploring%20the%20therapeutic%20role%20of%20creatine%20supplementation&author=B%20Gualano&author=GG%20Artioli&author=JR%20Poortmans&author=AH%20Lancha%20Junior&publication_year=2009&pmid=19253023&doi=10.1007/s00726-009-0263-6&)]; This new review investigates whether creatine supplementation could be used as a therapeutic tool for the elderly and summarizes the main studies conducted in this field, highlighting the scientific and clinical perspectives on the therapeutic potential of creatine.
  * 6.Lundholm K, Bennegard K, Eden E, et al. Efflux of 3-methylhistidine from the leg in cancer patients who experience weight loss. Cancer Res. 1982;42(11):4807–4811. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/7127315/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&title=Efflux%20of%203-methylhistidine%20from%20the%20leg%20in%20cancer%20patients%20who%20experience%20weight%20loss&author=K%20Lundholm&author=K%20Bennegard&author=E%20Eden&volume=42&issue=11&publication_year=1982&pages=4807-4811&pmid=7127315&)]
  * 7.Tipton KD, Ferrando AA. Improving muscle mass: response of muscle metabolism to exercise, nutrition and anabolic agents. Essays Biochem. 2008;44:85–98. doi: 10.1042/BSE0440085. [[DOI](https://doi.org/10.1042/BSE0440085)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18384284/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Essays%20Biochem&title=Improving%20muscle%20mass:%20response%20of%20muscle%20metabolism%20to%20exercise,%20nutrition%20and%20anabolic%20agents&author=KD%20Tipton&author=AA%20Ferrando&volume=44&publication_year=2008&pages=85-98&pmid=18384284&doi=10.1042/BSE0440085&)]
  * 8*.Sakkas GK, Mulligan K, Dasilva M, et al. Creatine fails to augment the benefits from resistance training in patients with HIV infection: a randomized, double-blind, placebo-controlled study. PLoS ONE. 2009;4(2):e4605. doi: 10.1371/journal.pone.0004605. [[DOI](https://doi.org/10.1371/journal.pone.0004605)] [[PMC free article](/articles/PMC2646129/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19242554/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=PLoS%20ONE&title=Creatine%20fails%20to%20augment%20the%20benefits%20from%20resistance%20training%20in%20patients%20with%20HIV%20infection:%20a%20randomized,%20double-blind,%20placebo-controlled%20study&author=GK%20Sakkas&author=K%20Mulligan&author=M%20Dasilva&volume=4&issue=2&publication_year=2009&pages=e4605&pmid=19242554&doi=10.1371/journal.pone.0004605&)]; This randomized, double-blind, placebo controlled study in HIV infected patients undergoing resistance exercise training showed a positive effect of creatine supplementation on lean body mass but no apparent functional benefit, assessed as muscle strength or intramuscular phosphocreatine metabolism during exercise.
  * 9.Cribb PJ, Hayes A. Effects of supplement timing and resistance exercise on skeletal muscle hypertrophy. Med Sci Sports Exerc. 2006;38(11):1918–1925. doi: 10.1249/01.mss.0000233790.08788.3e. [[DOI](https://doi.org/10.1249/01.mss.0000233790.08788.3e)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17095924/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Med%20Sci%20Sports%20Exerc&title=Effects%20of%20supplement%20timing%20and%20resistance%20exercise%20on%20skeletal%20muscle%20hypertrophy&author=PJ%20Cribb&author=A%20Hayes&volume=38&issue=11&publication_year=2006&pages=1918-1925&pmid=17095924&doi=10.1249/01.mss.0000233790.08788.3e&)]
  * 10.Safdar A, Yardley NJ, Snow R, et al. Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics. 2008;32(2):219–228. doi: 10.1152/physiolgenomics.00157.2007. [[DOI](https://doi.org/10.1152/physiolgenomics.00157.2007)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17957000/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Physiol%20Genomics&title=Global%20and%20targeted%20gene%20expression%20and%20protein%20content%20in%20skeletal%20muscle%20of%20young%20men%20following%20short-term%20creatine%20monohydrate%20supplementation&author=A%20Safdar&author=NJ%20Yardley&author=R%20Snow&volume=32&issue=2&publication_year=2008&pages=219-228&pmid=17957000&doi=10.1152/physiolgenomics.00157.2007&)]
  * 11.Kley RA, Vorgerd M, Tarnopolsky MA. Creatine for treating muscle disorders. Cochrane Database Syst Rev. 2007;(1):CD004760. doi: 10.1002/14651858.CD004760.pub2. [[DOI](https://doi.org/10.1002/14651858.CD004760.pub2)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17253521/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cochrane%20Database%20Syst%20Rev&title=Creatine%20for%20treating%20muscle%20disorders&author=RA%20Kley&author=M%20Vorgerd&author=MA%20Tarnopolsky&issue=1&publication_year=2007&pages=CD004760&pmid=17253521&doi=10.1002/14651858.CD004760.pub2&)]
  * 12.Tarnopolsky MA. Clinical use of creatine in neuromuscular and neurometabolic disorders. Subcell Biochem. 2007;46:183–204. doi: 10.1007/978-1-4020-6486-9_10. [[DOI](https://doi.org/10.1007/978-1-4020-6486-9_10)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18652078/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Subcell%20Biochem&title=Clinical%20use%20of%20creatine%20in%20neuromuscular%20and%20neurometabolic%20disorders&author=MA%20Tarnopolsky&volume=46&publication_year=2007&pages=183-204&pmid=18652078&doi=10.1007/978-1-4020-6486-9_10&)]
  * 13.Earnest CP, Snell PG, Rodriguez R, et al. The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand. 1995;153(2):207–209. doi: 10.1111/j.1748-1716.1995.tb09854.x. [[DOI](https://doi.org/10.1111/j.1748-1716.1995.tb09854.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/7778463/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Acta%20Physiol%20Scand&title=The%20effect%20of%20creatine%20monohydrate%20ingestion%20on%20anaerobic%20power%20indices,%20muscular%20strength%20and%20body%20composition&author=CP%20Earnest&author=PG%20Snell&author=R%20Rodriguez&volume=153&issue=2&publication_year=1995&pages=207-209&pmid=7778463&doi=10.1111/j.1748-1716.1995.tb09854.x&)]
  * 14.Kreider RB, Ferreira M, Wilson M, et al. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc. 1998;30(1):73–82. doi: 10.1097/00005768-199801000-00011. [[DOI](https://doi.org/10.1097/00005768-199801000-00011)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9475647/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Med%20Sci%20Sports%20Exerc&title=Effects%20of%20creatine%20supplementation%20on%20body%20composition,%20strength,%20and%20sprint%20performance&author=RB%20Kreider&author=M%20Ferreira&author=M%20Wilson&volume=30&issue=1&publication_year=1998&pages=73-82&pmid=9475647&doi=10.1097/00005768-199801000-00011&)]
  * 15.Hespel P, Op't EijndeB, Van Leemputte M, et al. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol. 2001;15536(Pt 2):625–633. doi: 10.1111/j.1469-7793.2001.0625c.xd. [[DOI](https://doi.org/10.1111/j.1469-7793.2001.0625c.xd)] [[PMC free article](/articles/PMC2278864/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11600695/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Physiol&title=Oral%20creatine%20supplementation%20facilitates%20the%20rehabilitation%20of%20disuse%20atrophy%20and%20alters%20the%20expression%20of%20muscle%20myogenic%20factors%20in%20humans&author=P%20Hespel&author=EijndeB%20Op't&author=M%20Van%20Leemputte&volume=15&issue=Pt%202&publication_year=2001&pages=625-633&pmid=11600695&doi=10.1111/j.1469-7793.2001.0625c.xd&)]
  * 16.Volek JS, Ratamess NA, Rubin MR, et al. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur J Appl Physiol. 2004;91(5-6):628–637. doi: 10.1007/s00421-003-1031-z. [[DOI](https://doi.org/10.1007/s00421-003-1031-z)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/14685870/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20J%20Appl%20Physiol&title=The%20effects%20of%20creatine%20supplementation%20on%20muscular%20performance%20and%20body%20composition%20responses%20to%20short-term%20resistance%20training%20overreaching&author=JS%20Volek&author=NA%20Ratamess&author=MR%20Rubin&volume=91&issue=5-6&publication_year=2004&pages=628-637&pmid=14685870&doi=10.1007/s00421-003-1031-z&)]
  * 17.Volek JS, Kraemer WJ, Bush JA, et al. Creatine supplementation enhances muscular performance during high-intensity resistance exercise. J Am Diet Assoc. 1997;97(7):765–770. doi: 10.1016/S0002-8223(97)00189-2. [[DOI](https://doi.org/10.1016/S0002-8223\(97\)00189-2)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9216554/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Am%20Diet%20Assoc&title=Creatine%20supplementation%20enhances%20muscular%20performance%20during%20high-intensity%20resistance%20exercise&author=JS%20Volek&author=WJ%20Kraemer&author=JA%20Bush&volume=97&issue=7&publication_year=1997&pages=765-770&pmid=9216554&doi=10.1016/S0002-8223\(97\)00189-2&)]
  * 18.Smith SA, Montain SJ, Matott RP, et al. Effects of creatine supplementation on the energy cost of muscle contraction: a 31P-MRS study. J Appl Physiol. 1999;87(1):116–123. doi: 10.1152/jappl.1999.87.1.116. [[DOI](https://doi.org/10.1152/jappl.1999.87.1.116)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10409565/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Appl%20Physiol&title=Effects%20of%20creatine%20supplementation%20on%20the%20energy%20cost%20of%20muscle%20contraction:%20a%2031P-MRS%20study&author=SA%20Smith&author=SJ%20Montain&author=RP%20Matott&volume=87&issue=1&publication_year=1999&pages=116-123&pmid=10409565&doi=10.1152/jappl.1999.87.1.116&)]
  * 19.Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol. 1994;266(5 Pt 1):E725–730. doi: 10.1152/ajpendo.1994.266.5.E725. [[DOI](https://doi.org/10.1152/ajpendo.1994.266.5.E725)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8203511/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Am%20J%20Physiol&title=Effect%20of%20oral%20creatine%20supplementation%20on%20skeletal%20muscle%20phosphocreatine%20resynthesis&author=PL%20Greenhaff&author=K%20Bodin&author=K%20Soderlund&author=E%20Hultman&volume=266&issue=5%20Pt%201&publication_year=1994&pages=E725-730&pmid=8203511&doi=10.1152/ajpendo.1994.266.5.E725&)]
  * 20.Culpepper RM. Creatine supplementation: safe as steak? South Med J. 1998;91(9):890–892. doi: 10.1097/00007611-199809000-00032. [[DOI](https://doi.org/10.1097/00007611-199809000-00032)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9743068/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=South%20Med%20J&title=Creatine%20supplementation:%20safe%20as%20steak?&author=RM%20Culpepper&volume=91&issue=9&publication_year=1998&pages=890-892&pmid=9743068&doi=10.1097/00007611-199809000-00032&)]
  * 21.Snow RJ, McKenna MJ, Selig SE, et al. Effect of creatine supplementation on sprint exercise performance and muscle metabolism. J Appl Physiol. 1998;84(5):1667–1673. doi: 10.1152/jappl.1998.84.5.1667. [[DOI](https://doi.org/10.1152/jappl.1998.84.5.1667)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9572815/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Appl%20Physiol&title=Effect%20of%20creatine%20supplementation%20on%20sprint%20exercise%20performance%20and%20muscle%20metabolism&author=RJ%20Snow&author=MJ%20McKenna&author=SE%20Selig&volume=84&issue=5&publication_year=1998&pages=1667-1673&pmid=9572815&doi=10.1152/jappl.1998.84.5.1667&)]
  * 22.Kinugasa R, Akima H, Ota A, et al. Short-term creatine supplementation does not improve muscle activation or sprint performance in humans. Eur J Appl Physiol. 2004;91(2-3):230–237. doi: 10.1007/s00421-003-0970-8. [[DOI](https://doi.org/10.1007/s00421-003-0970-8)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/14574579/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20J%20Appl%20Physiol&title=Short-term%20creatine%20supplementation%20does%20not%20improve%20muscle%20activation%20or%20sprint%20performance%20in%20humans&author=R%20Kinugasa&author=H%20Akima&author=A%20Ota&volume=91&issue=2-3&publication_year=2004&pages=230-237&pmid=14574579&doi=10.1007/s00421-003-0970-8&)]
  * 23.Syrotuik DG, Bell GJ. Acute creatine monohydrate supplementation: a descriptive physiological profile of responders vs. nonresponders. J Strength Cond Res. 2004;18(3):610–617. doi: 10.1519/12392.1. [[DOI](https://doi.org/10.1519/12392.1)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/15320650/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Strength%20Cond%20Res&title=Acute%20creatine%20monohydrate%20supplementation:%20a%20descriptive%20physiological%20profile%20of%20responders%20vs.%20nonresponders&author=DG%20Syrotuik&author=GJ%20Bell&volume=18&issue=3&publication_year=2004&pages=610-617&pmid=15320650&doi=10.1519/12392.1&)]
  * 24.Komura K, Hobbiebrunken E, Wilichowski EK, Hanefeld FA. Effectiveness of creatine monohydrate in mitochondrial encephalomyopathies. Pediatr Neurol. 2003;28(1):53–58. doi: 10.1016/s0887-8994(02)00469-1. [[DOI](https://doi.org/10.1016/s0887-8994\(02\)00469-1)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/12657421/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Pediatr%20Neurol&title=Effectiveness%20of%20creatine%20monohydrate%20in%20mitochondrial%20encephalomyopathies&author=K%20Komura&author=E%20Hobbiebrunken&author=EK%20Wilichowski&author=FA%20Hanefeld&volume=28&issue=1&publication_year=2003&pages=53-58&pmid=12657421&doi=10.1016/s0887-8994\(02\)00469-1&)]
  * 25.Tarnopolsky MA, Roy BD, MacDonald JR. A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve. 1997;20(12):1502–1509. doi: 10.1002/(sici)1097-4598(199712)20:12<1502::aid-mus4>3.0.co;2-c. [[DOI](https://doi.org/10.1002/\(sici\)1097-4598\(199712\)20:12<1502::aid-mus4>3.0.co;2-c)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9390662/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Muscle%20Nerve&title=A%20randomized,%20controlled%20trial%20of%20creatine%20monohydrate%20in%20patients%20with%20mitochondrial%20cytopathies&author=MA%20Tarnopolsky&author=BD%20Roy&author=JR%20MacDonald&volume=20&issue=12&publication_year=1997&pages=1502-1509&pmid=9390662&doi=10.1002/\(sici\)1097-4598\(199712\)20:12<1502::aid-mus4>3.0.co;2-c&)]
  * 26.Gordon A, Hultman E, Kaijser L, et al. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res. 1995;30(3):413–418. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/7585833/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cardiovasc%20Res&title=Creatine%20supplementation%20in%20chronic%20heart%20failure%20increases%20skeletal%20muscle%20creatine%20phosphate%20and%20muscle%20performance&author=A%20Gordon&author=E%20Hultman&author=L%20Kaijser&volume=30&issue=3&publication_year=1995&pages=413-418&pmid=7585833&)]
  * 27.Tarnopolsky MA, Mahoney DJ, Vajsar J, et al. Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy. Neurology. 2004;62(10):1771–1777. doi: 10.1212/01.wnl.0000125178.18862.9d. [[DOI](https://doi.org/10.1212/01.wnl.0000125178.18862.9d)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/15159476/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Neurology&title=Creatine%20monohydrate%20enhances%20strength%20and%20body%20composition%20in%20Duchenne%20muscular%20dystrophy&author=MA%20Tarnopolsky&author=DJ%20Mahoney&author=J%20Vajsar&volume=62&issue=10&publication_year=2004&pages=1771-1777&pmid=15159476&doi=10.1212/01.wnl.0000125178.18862.9d&)]
  * 28.Walter MC, Lochmuller H, Reilich P, et al. Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study. Neurology. 2000;54(9):1848–1850. doi: 10.1212/wnl.54.9.1848. [[DOI](https://doi.org/10.1212/wnl.54.9.1848)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10802796/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Neurology&title=Creatine%20monohydrate%20in%20muscular%20dystrophies:%20A%20double-blind,%20placebo-controlled%20clinical%20study&author=MC%20Walter&author=H%20Lochmuller&author=P%20Reilich&volume=54&issue=9&publication_year=2000&pages=1848-1850&pmid=10802796&doi=10.1212/wnl.54.9.1848&)]
  * 29.Tarnopolsky M, Zimmer A, Paikin J, et al. Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults. PLoS ONE. 2007;2(10):e991. doi: 10.1371/journal.pone.0000991. [[DOI](https://doi.org/10.1371/journal.pone.0000991)] [[PMC free article](/articles/PMC1994592/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17912368/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=PLoS%20ONE&title=Creatine%20monohydrate%20and%20conjugated%20linoleic%20acid%20improve%20strength%20and%20body%20composition%20following%20resistance%20exercise%20in%20older%20adults&author=M%20Tarnopolsky&author=A%20Zimmer&author=J%20Paikin&volume=2&issue=10&publication_year=2007&pages=e991&pmid=17912368&doi=10.1371/journal.pone.0000991&)]
  * 30.Vorgerd M, Grehl T, Jager M, et al. Creatine therapy for myophosphorylase deficiency (McArdle disease). A placebo-controlled crossover trial. Arch Neurol. 2000;57:956–963. doi: 10.1001/archneur.57.7.956. [[DOI](https://doi.org/10.1001/archneur.57.7.956)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10891977/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Arch%20Neurol&title=Creatine%20therapy%20for%20myophosphorylase%20deficiency%20\(McArdle%20disease\).%20A%20placebo-controlled%20crossover%20trial&author=M%20Vorgerd&author=T%20Grehl&author=M%20Jager&volume=57&publication_year=2000&pages=956-963&pmid=10891977&doi=10.1001/archneur.57.7.956&)]
  * 31.Tarnopolsky M, Mahoney D, Thompson T, et al. Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Muscle Nerve. 2004;29(1):51–58. doi: 10.1002/mus.10527. [[DOI](https://doi.org/10.1002/mus.10527)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/14694498/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Muscle%20Nerve&title=Creatine%20monohydrate%20supplementation%20does%20not%20increase%20muscle%20strength,%20lean%20body%20mass,%20or%20muscle%20phosphocreatine%20in%20patients%20with%20myotonic%20dystrophy%20type%201&author=M%20Tarnopolsky&author=D%20Mahoney&author=T%20Thompson&volume=29&issue=1&publication_year=2004&pages=51-58&pmid=14694498&doi=10.1002/mus.10527&)]
  * 32.Kornblum C, Schroder R, Muller K, et al. Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study. Eur J Neurol. 2005;12(4):300–309. doi: 10.1111/j.1468-1331.2004.00970.x. [[DOI](https://doi.org/10.1111/j.1468-1331.2004.00970.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/15804248/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20J%20Neurol&title=Creatine%20has%20no%20beneficial%20effect%20on%20skeletal%20muscle%20energy%20metabolism%20in%20patients%20with%20single%20mitochondrial%20DNA%20deletions:%20a%20placebo-controlled,%20double-blind%2031P-MRS%20crossover%20study&author=C%20Kornblum&author=R%20Schroder&author=K%20Muller&volume=12&issue=4&publication_year=2005&pages=300-309&pmid=15804248&doi=10.1111/j.1468-1331.2004.00970.x&)]
  * 33.Walter MC, Reilich P, Lochmuller H, et al. Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. J Neurol. 2002;249(12):1717–1722. doi: 10.1007/s00415-002-0923-x. [[DOI](https://doi.org/10.1007/s00415-002-0923-x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/12529796/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Neurol&title=Creatine%20monohydrate%20in%20myotonic%20dystrophy:%20a%20double-blind,%20placebo-controlled%20clinical%20study&author=MC%20Walter&author=P%20Reilich&author=H%20Lochmuller&volume=249&issue=12&publication_year=2002&pages=1717-1722&pmid=12529796&doi=10.1007/s00415-002-0923-x&)]
  * 34.Vorgerd M, Zange J, Kley R, et al. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease. Double-blind, placebo-controlled crossover study. Arch Neurol. 2002;59:97–101. doi: 10.1001/archneur.59.1.97. [[DOI](https://doi.org/10.1001/archneur.59.1.97)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11790236/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Arch%20Neurol&title=Effect%20of%20high-dose%20creatine%20therapy%20on%20symptoms%20of%20exercise%20intolerance%20in%20McArdle%20disease.%20Double-blind,%20placebo-controlled%20crossover%20study&author=M%20Vorgerd&author=J%20Zange&author=R%20Kley&volume=59&publication_year=2002&pages=97-101&pmid=11790236&doi=10.1001/archneur.59.1.97&)]
  * 35.Zange J, Kornblum C, Muller K, et al. Creatine supplementation results in elevated phosphocreatine/adenosine triphosphate (ATP) ratios in the calf muscle of athletes but not in patients with myopathies. Ann Neurol. 2002;52(1):126. doi: 10.1002/ana.10197. author reply 126-127. [[DOI](https://doi.org/10.1002/ana.10197)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/12112063/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Ann%20Neurol&title=Creatine%20supplementation%20results%20in%20elevated%20phosphocreatine/adenosine%20triphosphate%20\(ATP\)%20ratios%20in%20the%20calf%20muscle%20of%20athletes%20but%20not%20in%20patients%20with%20myopathies&author=J%20Zange&author=C%20Kornblum&author=K%20Muller&volume=52&issue=1&publication_year=2002&pages=126&pmid=12112063&doi=10.1002/ana.10197&)]
  * 36*.Johnston AP, Burke DG, MacNeil LG, Candow DG. Effect of creatine supplementation during cast-induced immobilization on the preservation of muscle mass, strength, and endurance. J Strength Cond Res. 2009;23(1):116–120. doi: 10.1519/jsc.0b013e31818efbcc. [[DOI](https://doi.org/10.1519/jsc.0b013e31818efbcc)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19130643/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Strength%20Cond%20Res&title=Effect%20of%20creatine%20supplementation%20during%20cast-induced%20immobilization%20on%20the%20preservation%20of%20muscle%20mass,%20strength,%20and%20endurance&author=AP%20Johnston&author=DG%20Burke&author=LG%20MacNeil&author=DG%20Candow&volume=23&issue=1&publication_year=2009&pages=116-120&pmid=19130643&doi=10.1519/jsc.0b013e31818efbcc&)]; This is the first study to demonstrate that short-term creatine supplementation attenuates the loss in muscle mass and strength during upper-arm immobilization in humans.
  * 37.Olsen S, Aagaard P, Kadi F, et al. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J Physiol. 2006;573(Pt 2):525–534. doi: 10.1113/jphysiol.2006.107359. [[DOI](https://doi.org/10.1113/jphysiol.2006.107359)] [[PMC free article](/articles/PMC1779717/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16581862/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Physiol&title=Creatine%20supplementation%20augments%20the%20increase%20in%20satellite%20cell%20and%20myonuclei%20number%20in%20human%20skeletal%20muscle%20induced%20by%20strength%20training&author=S%20Olsen&author=P%20Aagaard&author=F%20Kadi&volume=573&issue=Pt%202&publication_year=2006&pages=525-534&pmid=16581862&doi=10.1113/jphysiol.2006.107359&)]
  * 38.Willoughby DS, Rosene J. Effects of oral creatine and resistance training on myosin heavy chain expression. Med Sci Sports Exerc. 2001;33(10):1674–1681. doi: 10.1097/00005768-200110000-00010. [[DOI](https://doi.org/10.1097/00005768-200110000-00010)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11581551/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Med%20Sci%20Sports%20Exerc&title=Effects%20of%20oral%20creatine%20and%20resistance%20training%20on%20myosin%20heavy%20chain%20expression&author=DS%20Willoughby&author=J%20Rosene&volume=33&issue=10&publication_year=2001&pages=1674-1681&pmid=11581551&doi=10.1097/00005768-200110000-00010&)]
  * 39.Strasser F. Appraisal of current and experimental approaches to the treatment of cachexia. Curr Opin Support Palliat Care. 2007;1(4):312–316. doi: 10.1097/SPC.0b013e3282f3474c. [[DOI](https://doi.org/10.1097/SPC.0b013e3282f3474c)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18685381/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Curr%20Opin%20Support%20Palliat%20Care&title=Appraisal%20of%20current%20and%20experimental%20approaches%20to%20the%20treatment%20of%20cachexia&author=F%20Strasser&volume=1&issue=4&publication_year=2007&pages=312-316&pmid=18685381&doi=10.1097/SPC.0b013e3282f3474c&)]
  * 40.Francaux M, Poortmans JR. Side effects of creatine supplementation in athletes. Int J Sports Physiol Perform. 2006;1(4):311–323. doi: 10.1123/ijspp.1.4.311. [[DOI](https://doi.org/10.1123/ijspp.1.4.311)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19124889/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Sports%20Physiol%20Perform&title=Side%20effects%20of%20creatine%20supplementation%20in%20athletes&author=M%20Francaux&author=JR%20Poortmans&volume=1&issue=4&publication_year=2006&pages=311-323&pmid=19124889&doi=10.1123/ijspp.1.4.311&)]
  * 41.Menezes LG, Sobreira C, Neder L, et al. Creatine supplementation attenuates corticosteroid-induced muscle wasting and impairment of exercise performance in rats. J Appl Physiol. 2007;102(2):698–703. doi: 10.1152/japplphysiol.01188.2005. [[DOI](https://doi.org/10.1152/japplphysiol.01188.2005)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17053101/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Appl%20Physiol&title=Creatine%20supplementation%20attenuates%20corticosteroid-induced%20muscle%20wasting%20and%20impairment%20of%20exercise%20performance%20in%20rats&author=LG%20Menezes&author=C%20Sobreira&author=L%20Neder&volume=102&issue=2&publication_year=2007&pages=698-703&pmid=17053101&doi=10.1152/japplphysiol.01188.2005&)]
  * 42.Hespel P, Derave W. Ergogenic effects of creatine in sports and rehabilitation. Subcell Biochem. 2007;46:245–259. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18652080/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Subcell%20Biochem&title=Ergogenic%20effects%20of%20creatine%20in%20sports%20and%20rehabilitation&author=P%20Hespel&author=W%20Derave&volume=46&publication_year=2007&pages=245-259&pmid=18652080&)]
  * 43.Yu Z, Li P, Zhang M, et al. Fiber type-specific nitric oxide protects oxidative myofibers against cachectic stimuli. PLoS ONE. 2008;3(5):e2086. doi: 10.1371/journal.pone.0002086. [[DOI](https://doi.org/10.1371/journal.pone.0002086)] [[PMC free article](/articles/PMC2361191/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18461174/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=PLoS%20ONE&title=Fiber%20type-specific%20nitric%20oxide%20protects%20oxidative%20myofibers%20against%20cachectic%20stimuli&author=Z%20Yu&author=P%20Li&author=M%20Zhang&volume=3&issue=5&publication_year=2008&pages=e2086&pmid=18461174&doi=10.1371/journal.pone.0002086&)]
  * 44.Morley JE, Anker SD, Evans WJ. Cachexia and aging: an update based on the Fourth International Cachexia Meeting. J Nutr Health Aging. 2009;13(1):47–55. doi: 10.1007/s12603-009-0009-x. [[DOI](https://doi.org/10.1007/s12603-009-0009-x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19151908/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Nutr%20Health%20Aging&title=Cachexia%20and%20aging:%20an%20update%20based%20on%20the%20Fourth%20International%20Cachexia%20Meeting&author=JE%20Morley&author=SD%20Anker&author=WJ%20Evans&volume=13&issue=1&publication_year=2009&pages=47-55&pmid=19151908&doi=10.1007/s12603-009-0009-x&)]
  * 45*.Bassit RA, Curi R, Costa Rosa LF. Creatine supplementation reduces plasma levels of pro-inflammatory cytokines and PGE2 after a half-ironman competition. Amino Acids. 2008;35(2):425–431. doi: 10.1007/s00726-007-0582-4. [[DOI](https://doi.org/10.1007/s00726-007-0582-4)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17917696/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Amino%20Acids&title=Creatine%20supplementation%20reduces%20plasma%20levels%20of%20pro-inflammatory%20cytokines%20and%20PGE2%20after%20a%20half-ironman%20competition&author=RA%20Bassit&author=R%20Curi&author=LF%20Costa%20Rosa&volume=35&issue=2&publication_year=2008&pages=425-431&pmid=17917696&doi=10.1007/s00726-007-0582-4&)]; This is the first study to show a positive effect of creatine supplementation on plasma levels of pro-inflammatory cytokines.
  * 46*.Gualano B, Novaes RB, Artioli GG, et al. Effects of creatine supplementation on glucose tolerance and insulin sensitivity in sedentary healthy males undergoing aerobic training. Amino Acids. 2008;34(2):245–250. doi: 10.1007/s00726-007-0508-1. [[DOI](https://doi.org/10.1007/s00726-007-0508-1)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17396216/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Amino%20Acids&title=Effects%20of%20creatine%20supplementation%20on%20glucose%20tolerance%20and%20insulin%20sensitivity%20in%20sedentary%20healthy%20males%20undergoing%20aerobic%20training&author=B%20Gualano&author=RB%20Novaes&author=GG%20Artioli&volume=34&issue=2&publication_year=2008&pages=245-250&pmid=17396216&doi=10.1007/s00726-007-0508-1&)]; This study suggests that creatine supplementation, combined with aerobic training, can improve glucose tolerance but does not affect insulin sensitivity in healthy subjects.
  * 47.Op 't Eijnde B, Urso B, Richter EA, et al. Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization. Diabetes. 2001;50(1):18–23. doi: 10.2337/diabetes.50.1.18. [[DOI](https://doi.org/10.2337/diabetes.50.1.18)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11147785/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Diabetes&title=Effect%20of%20oral%20creatine%20supplementation%20on%20human%20muscle%20GLUT4%20protein%20content%20after%20immobilization&author=B%20Op%20't%20Eijnde&author=B%20Urso&author=EA%20Richter&volume=50&issue=1&publication_year=2001&pages=18-23&pmid=11147785&doi=10.2337/diabetes.50.1.18&)]
  * 48.Galbraith RA, Furukawa M, Li M. Possible role of creatine concentrations in the brain in regulating appetite and weight. Brain Res. 2006;1101(1):85–91. doi: 10.1016/j.brainres.2006.05.032. [[DOI](https://doi.org/10.1016/j.brainres.2006.05.032)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16781683/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Brain%20Res&title=Possible%20role%20of%20creatine%20concentrations%20in%20the%20brain%20in%20regulating%20appetite%20and%20weight&author=RA%20Galbraith&author=M%20Furukawa&author=M%20Li&volume=1101&issue=1&publication_year=2006&pages=85-91&pmid=16781683&doi=10.1016/j.brainres.2006.05.032&)]
  * 49.Buford TW, Kreider RB, Stout JR, et al. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr. 2007;4:6. doi: 10.1186/1550-2783-4-6. [[DOI](https://doi.org/10.1186/1550-2783-4-6)] [[PMC free article](/articles/PMC2048496/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17908288/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Int%20Soc%20Sports%20Nutr&title=International%20Society%20of%20Sports%20Nutrition%20position%20stand:%20creatine%20supplementation%20and%20exercise&author=TW%20Buford&author=RB%20Kreider&author=JR%20Stout&volume=4&publication_year=2007&pages=6&pmid=17908288&doi=10.1186/1550-2783-4-6&)]
  * 50.Pline KA, Smith CL. The effect of creatine intake on renal function. Ann Pharmacother. 2005;39(6):1093–1096. doi: 10.1345/aph.1E628. [[DOI](https://doi.org/10.1345/aph.1E628)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/15886291/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Ann%20Pharmacother&title=The%20effect%20of%20creatine%20intake%20on%20renal%20function&author=KA%20Pline&author=CL%20Smith&volume=39&issue=6&publication_year=2005&pages=1093-1096&pmid=15886291&doi=10.1345/aph.1E628&)]



![Close](/static/img/usa-icons/close.svg)

## ACTIONS

  * [ View on publisher site ](https://doi.org/10.1097/MCO.0b013e328331de63)
  * [ PDF (57.4 KB) ](pdf/nihms202834.pdf)
  * Cite
  * Collections
  * Permalink

## PERMALINK

Copy




## RESOURCES

###  Similar articles 

###  Cited by other articles 

###  Links to NCBI Databases 

## Cite

  * Copy
  * Download .nbib .nbib
  * Format: AMA  APA  MLA  NLM 




## Add to Collections

Create a new collection

Add to an existing collection

Name your collection *

Choose a collection 

Unable to load your collection due to an error  
Please try again

Add  Cancel 

Follow NCBI 

[ NCBI on X (formerly known as Twitter) ](https://twitter.com/ncbi) [ NCBI on Facebook ](https://www.facebook.com/ncbi.nlm) [ NCBI on LinkedIn ](https://www.linkedin.com/company/ncbinlm) [ NCBI on GitHub ](https://github.com/ncbi) [ NCBI RSS feed ](https://ncbiinsights.ncbi.nlm.nih.gov/)

Connect with NLM 

[ NLM on X (formerly known as Twitter) ](https://twitter.com/nlm_nih) [ NLM on Facebook ](https://www.facebook.com/nationallibraryofmedicine) [ NLM on YouTube ](https://www.youtube.com/user/NLMNIH)

[National Library of Medicine   
8600 Rockville Pike  
Bethesda, MD 20894](https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/%4038.9959508,
            -77.101021,17z/data%3D!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb%3A0x19156f88b27635b8!8m2!3d38.9959508!
            4d-77.0988323)

  * [ Web Policies ](https://www.nlm.nih.gov/web_policies.html)
  * [ FOIA ](https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office)
  * [ HHS Vulnerability Disclosure ](https://www.hhs.gov/vulnerability-disclosure-policy/index.html)


  * [ Help ](https://support.nlm.nih.gov/)
  * [ Accessibility ](https://www.nlm.nih.gov/accessibility.html)
  * [ Careers ](https://www.nlm.nih.gov/careers/careers.html)



  * [ NLM ](https://www.nlm.nih.gov/)
  * [ NIH ](https://www.nih.gov/)
  * [ HHS ](https://www.hhs.gov/)
  * [ USA.gov ](https://www.usa.gov/)



Back to Top
  *[*]: required


url: https://pubmed.ncbi.nlm.nih.gov/39401279/
scrape_date: 2025-02-28T09:09:39.085897
content_type: markdown
hash: c9feec913a654000c00ee60ff4e69f903443813406c491e0602e227b24791e47
title:
Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss? - PubMed

content:
This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! 

Clipboard, Search History, and several other advanced features are temporarily unavailable. 

Skip to main page content 

![U.S. flag](https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png)

An official website of the United States government

Here's how you know

![Dot gov](https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg)

**The .gov means it’s official.**   
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site. 

![Https](https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg)

**The site is secure.**   
The **https://** ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. 

[ ![NIH NLM Logo](https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg) ](https://www.ncbi.nlm.nih.gov/)

[Log in](https://account.ncbi.nlm.nih.gov) Show account info

Close

#### Account

Logged in as:  
**username**

  * [Dashboard](/myncbi/)
  * [Publications](/myncbi/collections/bibliography/)
  * [Account settings](/account/settings/)
  * [Log out](/account/signout/)



[Access keys](https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys) [NCBI Homepage](https://www.ncbi.nlm.nih.gov) [MyNCBI Homepage](/myncbi/) Main Content Main Navigation

[ ![pubmed logo](https://cdn.ncbi.nlm.nih.gov/pubmed/1aadf23f-d23c-47f2-9ae5-722feb08e2c5/core/images/pubmed-logo-blue.svg) ](/)

Search:  Search

[Advanced](/advanced/) [ Clipboard  ](/clipboard/)

[ User Guide ](/help/)

Save  Email 

Send to

  * Clipboard 
  * [My Bibliography](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F39401279%2F%23open-bibliography-panel)
  * [Collections](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F39401279%2F%23open-collections-panel)
  * Citation manager



Display options

Display options 

Format  Abstract PubMed PMID

##  Save citation to file 

Format:  Summary (text) PubMed PMID Abstract (text) CSV

Create file  Cancel 

##  Email citation 

Subject:  1 selected item: 39401279 - PubMed

To: 

From: 

Format:  Summary Summary (text) Abstract Abstract (text)

MeSH and other data

Send email  Cancel 

###  Add to Collections 

  * Create a new collection
  * Add to an existing collection



Name your collection: 

Name must be less than 100 characters 

Choose a collection: 

Unable to load your collection due to an error  
Please try again

Add  Cancel 

###  Add to My Bibliography 

  * My Bibliography



Unable to load your delegates due to an error  
Please try again

Add  Cancel 

##  Your saved search 

Name of saved search: 

Search terms: 

Test search terms

Would you like email updates of new search results?  Saved Search Alert Radio Buttons

  * Yes
  * No



Email:  ([change](https://www.ncbi.nlm.nih.gov/account/settings/))

Frequency:  Monthly Weekly Daily

Which day?  The first Sunday The first Monday The first Tuesday The first Wednesday The first Thursday The first Friday The first Saturday The first day The first weekday

Which day?  Sunday Monday Tuesday Wednesday Thursday Friday Saturday

Report format:  Summary Summary (text) Abstract Abstract (text) PubMed

Send at most:  1 item 5 items 10 items 20 items 50 items 100 items 200 items

Send even when there aren't any new results 

Optional text in email: 

Save  Cancel 

##  Create a file for external citation management software 

Create file  Cancel 

##  Your RSS Feed 

Name of RSS Feed: 

Number of items displayed:  5 10 15 20 50 100

Create RSS  Cancel 

RSS Link Copy 

###  Full text links 

[![Atypon full text link](https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ahajournals.org-pb-assets-pubmed-images-CSA-circ.gif) Atypon ](https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.067676?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub  0pubmed "See full text options at Atypon")

Full text links 

### Actions

Cite

Collections

Add to Collections

  * Create a new collection
  * Add to an existing collection



Name your collection: 

Name must be less than 100 characters 

Choose a collection: 

Unable to load your collection due to an error  
Please try again

Add  Cancel 

Display options

Display options 

Format AbstractPubMedPMID

###  Share 

  * [](http://twitter.com/intent/tweet?text=Muscle%20Mass%20and%20Glucagon-Like%20Peptide-1%20Receptor%20Agonists%3A%20Adaptive%20or%20Maladaptive%20Response%20to%20Weight%20Loss%3F%20https%3A//pubmed.ncbi.nlm.nih.gov/39401279/ "Share article on Twitter")
  * [](http://www.facebook.com/sharer/sharer.php?u=https%3A//pubmed.ncbi.nlm.nih.gov/39401279/ "Share article on Facebook")
  * Permalink 

Copy




###  Page navigation 

  * Title & authors 
  * Abstract 
  * Conflict of interest statement 
  * Similar articles 
  * Publication types 
  * MeSH terms 
  * Substances 
  * Related information 
  * LinkOut - more resources 



Title & authors Abstract Conflict of interest statement Similar articles Publication types MeSH terms Substances Related information LinkOut - more resources

Review

Circulation 

Actions

  * [ Search in PubMed ](/?term=%22Circulation%22%5Bjour%5D&sort=date&sort_order=desc)
  * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Circulation%22%5BTitle+Abbreviation%5D)
  * Add to Search 



. 2024 Oct 15;150(16):1288-1298.

doi: 10.1161/CIRCULATIONAHA.124.067676.  Epub 2024 Oct 14. 

#  Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss? 

[Jennifer Linge](/?term=Linge+J&cauthor_id=39401279)  1   2 , [Andreas L Birkenfeld](/?term=Birkenfeld+AL&cauthor_id=39401279)  3   4   5   6 , [Ian J Neeland](/?term=Neeland+IJ&cauthor_id=39401279)  7   8 

Affiliations  Expand 

###  Affiliations 

  * 1 AMRA Medical AB, Linköping, Sweden (J.L.).
  * 2 Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Sweden (J.L.).
  * 3 Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Germany (A.L.B.).
  * 4 Department of Diabetology, Endocrinology, and Nephrology, University Clinic Tübingen, Eberhard Karls University Tübingen, Germany (A.L.B.).
  * 5 German Center for Diabetes Research (DZD), Neuherberg, Germany (A.L.B.).
  * 6 Department of Diabetes, Life Sciences & Medicine, Cardiovascular Medicine & Sciences, Kings College London, UK (A.L.B.).
  * 7 Division of Cardiovascular Medicine, University Hospitals Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, OH (I.J.N.).
  * 8 Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (I.J.N.).



  * PMID:  **39401279**
  * DOI:  [ 10.1161/CIRCULATIONAHA.124.067676 ](https://doi.org/10.1161/circulationaha.124.067676)



Item in Clipboard 

Review

#  Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss? 

Jennifer Linge et al. Circulation. 2024.

Show details

Display options

Display options 

Format  Abstract PubMed PMID

Circulation 

Actions

  * [ Search in PubMed ](/?term=%22Circulation%22%5Bjour%5D&sort=date&sort_order=desc)
  * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Circulation%22%5BTitle+Abbreviation%5D)
  * Add to Search 



. 2024 Oct 15;150(16):1288-1298.

doi: 10.1161/CIRCULATIONAHA.124.067676.  Epub 2024 Oct 14. 

###  Authors 

[Jennifer Linge](/?term=Linge+J&cauthor_id=39401279)  1   2 , [Andreas L Birkenfeld](/?term=Birkenfeld+AL&cauthor_id=39401279)  3   4   5   6 , [Ian J Neeland](/?term=Neeland+IJ&cauthor_id=39401279)  7   8 

###  Affiliations 

  * 1 AMRA Medical AB, Linköping, Sweden (J.L.).
  * 2 Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Sweden (J.L.).
  * 3 Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Germany (A.L.B.).
  * 4 Department of Diabetology, Endocrinology, and Nephrology, University Clinic Tübingen, Eberhard Karls University Tübingen, Germany (A.L.B.).
  * 5 German Center for Diabetes Research (DZD), Neuherberg, Germany (A.L.B.).
  * 6 Department of Diabetes, Life Sciences & Medicine, Cardiovascular Medicine & Sciences, Kings College London, UK (A.L.B.).
  * 7 Division of Cardiovascular Medicine, University Hospitals Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, OH (I.J.N.).
  * 8 Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (I.J.N.).



  * PMID:  **39401279**
  * DOI:  [ 10.1161/CIRCULATIONAHA.124.067676 ](https://doi.org/10.1161/circulationaha.124.067676)



Item in Clipboard 

Full text links Cite

Display options

Display options 

Format AbstractPubMedPMID

##  Abstract 

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future. 

**Keywords:** body composition; cardiovascular diseases; diabetes mellitus, type 2; glucagon-like peptide-1 receptor; insulin resistance; muscles; obesity; sarcopenia. 

[PubMed Disclaimer](/disclaimer/)

##  Conflict of interest statement 

Dr Neeland has received honoraria, consulting, and speaker’s bureau fees and travel support from Boehringer-Ingelheim/Lilly Alliance, consulting and speaker’s bureau fees from Bayer Pharmaceuticals, and consulting fees from Novo Nordisk, and has participated in scientific advisory boards for Lilly, Boehringer Ingelheim, Novo Nordisk, and AMRA Medical. Dr Birkenfeld has received consulting fees from Novo Nordisk and Bayer, as well as research support from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Lilly, and Daiichi Sankyo, all given to Tübingen University. Dr Linge is an employee and shareholder of AMRA Medical AB, has received consulting and travel support from Eli Lilly, and has received speaker’s bureau fees and travel support from BioMarin.

##  Similar articles 

  * [ Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. ](/38937282/)

Neeland IJ, Linge J, Birkenfeld AL. Neeland IJ, et al. Diabetes Obes Metab. 2024 Sep;26 Suppl 4:16-27. doi: 10.1111/dom.15728. Epub 2024 Jun 27. Diabetes Obes Metab. 2024. PMID: 38937282 Review.

  * [ Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight and Cardiometabolic Parameters in Individuals With Obesity and Without Diabetes: A Systematic Review and Meta-Analysis. ](/38029929/)

Ansari HUH, Qazi SU, Sajid F, Altaf Z, Ghazanfar S, Naveed N, Ashfaq AS, Siddiqui AH, Iqbal H, Qazi S. Ansari HUH, et al. Endocr Pract. 2024 Feb;30(2):160-171. doi: 10.1016/j.eprac.2023.11.007. Epub 2023 Nov 27. Endocr Pract. 2024. PMID: 38029929 Review.

  * [ The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective. ](/31260047/)

Jensterle M, Janez A, Fliers E, DeVries JH, Vrtacnik-Bokal E, Siegelaar SE. Jensterle M, et al. Hum Reprod Update. 2019 Jul 1;25(4):504-517. doi: 10.1093/humupd/dmz019. Hum Reprod Update. 2019. PMID: 31260047 Review.

  * [ Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity. ](/37999750/)

Herrou J, Mabilleau G, Lecerf JM, Thomas T, Biver E, Paccou J. Herrou J, et al. Calcif Tissue Int. 2024 Feb;114(2):86-97. doi: 10.1007/s00223-023-01150-8. Epub 2023 Nov 24. Calcif Tissue Int. 2024. PMID: 37999750 Review.

  * [ Opportunities to optimize lifestyle interventions in combination with glucagon-like peptide-1-based therapy. ](/39157881/)

Dash S. Dash S. Diabetes Obes Metab. 2024 Sep;26 Suppl 4:3-15. doi: 10.1111/dom.15829. Epub 2024 Aug 19. Diabetes Obes Metab. 2024. PMID: 39157881 Review.




See all similar articles 

##  Publication types 

  * Review 

Actions

    * [ Search in PubMed ](/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review)
    * Add to Search 




##  MeSH terms 

  * Adaptation, Physiological / drug effects 

Actions

    * [ Search in PubMed ](/?term=%22Adaptation%2C+Physiological%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adaptation%2C+Physiological)
    * Add to Search 

  * Animals 

Actions

    * [ Search in PubMed ](/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals)
    * Add to Search 

  * Glucagon-Like Peptide-1 Receptor Agonists* 

Actions

    * [ Search in PubMed ](/?term=%22Glucagon-Like+Peptide-1+Receptor+Agonists%22%5BMAJR%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Glucagon-Like+Peptide-1+Receptor+Agonists)
    * Add to Search 

  * Humans 

Actions

    * [ Search in PubMed ](/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans)
    * Add to Search 

  * Muscle, Skeletal* / drug effects 

Actions

    * [ Search in PubMed ](/?term=%22Muscle%2C+Skeletal%2Fdrug+effects%22%5BMAJR%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Muscle%2C+Skeletal)
    * Add to Search 

  * Muscle, Skeletal* / pathology 

Actions

    * [ Search in PubMed ](/?term=%22Muscle%2C+Skeletal%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Muscle%2C+Skeletal)
    * Add to Search 

  * Obesity / drug therapy 

Actions

    * [ Search in PubMed ](/?term=%22Obesity%2Fdrug+therapy%22%5BMeSH%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Obesity)
    * Add to Search 

  * Sarcopenia / drug therapy 

Actions

    * [ Search in PubMed ](/?term=%22Sarcopenia%2Fdrug+therapy%22%5BMeSH%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Sarcopenia)
    * Add to Search 

  * Weight Loss* / drug effects 

Actions

    * [ Search in PubMed ](/?term=%22Weight+Loss%2Fdrug+effects%22%5BMAJR%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Weight+Loss)
    * Add to Search 




##  Substances 

  * Glucagon-Like Peptide-1 Receptor Agonists 

Actions

    * [ Search in PubMed ](/?term=%22Glucagon-Like+Peptide-1+Receptor+Agonists%22%5Bnm%5D&sort=date&sort_order=desc)
    * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=%22Glucagon-Like+Peptide-1+Receptor+Agonists%22)
    * Add to Search 




##  Related information 

  * [ MedGen ](https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=39401279 "Related information in MedGen")



##  LinkOut - more resources 

  * ### Full Text Sources

    * [ Atypon ](https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.067676?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub  0pubmed)
    * [ Ovid Technologies, Inc. ](http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=39401279.ui)
  * ### Medical

    * [ MedlinePlus Consumer Health Information ](https://medlineplus.gov/weightcontrol.html)
    * [ MedlinePlus Health Information ](https://medlineplus.gov/weightcontrol.html)



**Full text links** [x]

[![Atypon full text link](https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ahajournals.org-pb-assets-pubmed-images-CSA-circ.gif) Atypon ](https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.067676?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub  0pubmed "See full text options at Atypon")

[x]

Cite

Copy  Download .nbib .nbib

Format: AMA  APA  MLA  NLM 

**Send To**

  * Clipboard
  * Email
  * Save
  * [My Bibliography](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F39401279%2F%23open-bibliography-panel)
  * [Collections](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F39401279%2F%23open-collections-panel)
  * Citation Manager

[x]

NCBI Literature Resources

[MeSH](https://www.ncbi.nlm.nih.gov/mesh/) [PMC](https://www.ncbi.nlm.nih.gov/pmc/) [Bookshelf](https://www.ncbi.nlm.nih.gov/books) [Disclaimer](/disclaimer/)

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Follow NCBI

[ Twitter ](https://twitter.com/ncbi) [ Facebook ](https://www.facebook.com/ncbi.nlm) [ LinkedIn ](https://www.linkedin.com/company/ncbinlm) [ GitHub ](https://github.com/ncbi) [ ](https://ncbiinsights.ncbi.nlm.nih.gov/)

[Connect with NLM](https://www.nlm.nih.gov/socialmedia/index.html)

  * [ Twitter ](https://twitter.com/NLM_NIH)
  * [ SM-Facebook ](https://www.facebook.com/nationallibraryofmedicine)
  * [ SM-Youtube ](https://www.youtube.com/user/NLMNIH)



National Library of Medicine  
[8600 Rockville Pike  
Bethesda, MD 20894](https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323)

[Web Policies](https://www.nlm.nih.gov/web_policies.html)  
[FOIA](https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office)  
[HHS Vulnerability Disclosure](https://www.hhs.gov/vulnerability-disclosure-policy/index.html)

[Help](https://support.nlm.nih.gov/)  
[Accessibility](https://www.nlm.nih.gov/accessibility.html)  
[Careers](https://www.nlm.nih.gov/careers/careers.html)

  * [NLM](//www.nlm.nih.gov/)
  * [NIH](https://www.nih.gov/)
  * [HHS](https://www.hhs.gov/)
  * [USA.gov](https://www.usa.gov/)


url: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1396656/full
scrape_date: 2025-02-28T09:09:39.595953
content_type: markdown
hash: 145ef5feda6f202b7f476e1f2af3f54d4b73acaa7e65a1eb03905576d6091782
title:
Frontiers | Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

content:
Skip to main content

[ ](//www.frontiersin.org/)

[![]() Frontiers in Pharmacology](//www.frontiersin.org/journals/pharmacology)

About us 

About us 

  * Who we are
  * [Mission and values](https://www.frontiersin.org/about/mission)
  * [History](https://www.frontiersin.org/about/history)
  * [Leadership](https://www.frontiersin.org/about/leadership)
  * [Awards](https://www.frontiersin.org/about/awards)


  * Impact and progress
  * [Frontiers' impact](https://www.frontiersin.org/about/impact)
  * [Progress Report 2022](https://progressreport.frontiersin.org/?utm_source=fweb&utm_medium=frep&utm_campaign=pr20)
  * [All annual reports](https://www.frontiersin.org/about/annual-reports)


  * Publishing model
  * [How we publish](https://www.frontiersin.org/about/how-we-publish)
  * [Open access](https://www.frontiersin.org/about/open-access)
  * [Fee policy](https://www.frontiersin.org/about/fee-policy)
  * [Peer review](https://www.frontiersin.org/about/peer-review)
  * [Research integrity](https://www.frontiersin.org/about/research-integrity)
  * [Research Topics](https://www.frontiersin.org/about/research-topics)


  * Services
  * [Societies](https://publishingpartnerships.frontiersin.org/)
  * [National consortia](https://www.frontiersin.org/open-access-agreements/consortia)
  * [Institutional partnerships](https://www.frontiersin.org/about/open-access-agreements)
  * [Collaborators](https://www.frontiersin.org/about/collaborators)


  * More from Frontiers
  * [Frontiers Forum](https://forum.frontiersin.org/)
  * [Frontiers Planet Prize](https://www.frontiersplanetprize.org/)
  * [Press office](https://pressoffice.frontiersin.org/)
  * [Sustainability](https://www.frontiersin.orgabout/sustainability)
  * [Career opportunities](https://careers.frontiersin.org/)
  * [Contact us](https://www.frontiersin.org/about/contact)



[All journals](https://www.frontiersin.org/journals)[All articles](https://www.frontiersin.org/articles) [Submit your research](https://www.frontiersin.org/submission/submit?domainid=1&fieldid=62&specialtyid=0&entitytype=2&entityid=176)

[Search](/search)

[ ](//www.frontiersin.org/)

[![]() Frontiers in Pharmacology](//www.frontiersin.org/journals/pharmacology)

Sections 

Sections 

  * [Cardiovascular and Smooth Muscle Pharmacology](/journals/pharmacology/sections/cardiovascular-and-smooth-muscle-pharmacology)
  * [Drug Metabolism and Transport](/journals/pharmacology/sections/drug-metabolism-and-transport)
  * [Drugs Outcomes Research and Policies](/journals/pharmacology/sections/drugs-outcomes-research-and-policies)
  * [ELSI in Science and Genetics](/journals/pharmacology/sections/elsi-in-science-and-genetics)
  * [Ethnopharmacology](/journals/pharmacology/sections/ethnopharmacology)
  * [Experimental Pharmacology and Drug Discovery](/journals/pharmacology/sections/experimental-pharmacology-and-drug-discovery)
  * [Gastrointestinal and Hepatic Pharmacology](/journals/pharmacology/sections/gastrointestinal-and-hepatic-pharmacology)
  * [Inflammation Pharmacology](/journals/pharmacology/sections/inflammation-pharmacology)
  * [Integrative and Regenerative Pharmacology](/journals/pharmacology/sections/integrative-and-regenerative-pharmacology)
  * [Neuropharmacology](/journals/pharmacology/sections/neuropharmacology)
  * [Obstetric and Pediatric Pharmacology](/journals/pharmacology/sections/obstetric-and-pediatric-pharmacology)
  * [Pharmacoepidemiology](/journals/pharmacology/sections/pharmacoepidemiology)
  * [Pharmacogenetics and Pharmacogenomics](/journals/pharmacology/sections/pharmacogenetics-and-pharmacogenomics)
  * [Pharmacology of Anti-Cancer Drugs](/journals/pharmacology/sections/pharmacology-of-anti-cancer-drugs)
  * [Pharmacology of Infectious Diseases](/journals/pharmacology/sections/pharmacology-of-infectious-diseases)
  * [Pharmacology of Ion Channels and Channelopathies](/journals/pharmacology/sections/pharmacology-of-ion-channels-and-channelopathies)
  * [Predictive Toxicology](/journals/pharmacology/sections/predictive-toxicology)
  * [Renal Pharmacology](/journals/pharmacology/sections/renal-pharmacology)
  * [Respiratory Pharmacology](/journals/pharmacology/sections/respiratory-pharmacology)
  * [Translational Pharmacology](/journals/pharmacology/sections/translational-pharmacology)



[Articles](//www.frontiersin.org/journals/pharmacology/articles)[Research Topics](//www.frontiersin.org/journals/pharmacology/research-topics)[Editorial board](//www.frontiersin.org/journals/pharmacology/editors)

About journal 

About journal 

  * Scope
  * [Field chief editors](https://www.frontiersin.org/journals/pharmacology/about#about-editors)
  * [Mission & scope](https://www.frontiersin.org/journals/pharmacology/about#about-scope)
  * [Facts](https://www.frontiersin.org/journals/pharmacology/about#about-facts)
  * [Journal sections](https://www.frontiersin.org/journals/pharmacology/about#about-submission)
  * [Open access statement](https://www.frontiersin.org/journals/pharmacology/about#about-open)
  * [Copyright statement](https://www.frontiersin.org/journals/pharmacology/about#copyright-statement)
  * [Quality](https://www.frontiersin.org/journals/pharmacology/about#about-quality)


  * For authors
  * [Why submit?](https://www.frontiersin.org/journals/pharmacology/for-authors/why-submit)
  * [Article types](https://www.frontiersin.org/journals/pharmacology/for-authors/article-types)
  * [Author guidelines](https://www.frontiersin.org/journals/pharmacology/for-authors/author-guidelines)
  * [Editor guidelines](https://www.frontiersin.org/journals/pharmacology/for-authors/editor-guidelines)
  * [Publishing fees](https://www.frontiersin.org/journals/pharmacology/for-authors/publishing-fees)
  * [Submission checklist](https://www.frontiersin.org/journals/pharmacology/for-authors/submission-checklist)
  * [Contact editorial office](https://www.frontiersin.org/journals/pharmacology/for-authors/contact-editorial-office)



About us 

About us 

  * Who we are
  * [Mission and values](https://www.frontiersin.org/about/mission)
  * [History](https://www.frontiersin.org/about/history)
  * [Leadership](https://www.frontiersin.org/about/leadership)
  * [Awards](https://www.frontiersin.org/about/awards)


  * Impact and progress
  * [Frontiers' impact](https://www.frontiersin.org/about/impact)
  * [Progress Report 2022](https://progressreport.frontiersin.org/?utm_source=fweb&utm_medium=frep&utm_campaign=pr20)
  * [All annual reports](https://www.frontiersin.org/about/annual-reports)


  * Publishing model
  * [How we publish](https://www.frontiersin.org/about/how-we-publish)
  * [Open access](https://www.frontiersin.org/about/open-access)
  * [Fee policy](https://www.frontiersin.org/about/fee-policy)
  * [Peer review](https://www.frontiersin.org/about/peer-review)
  * [Research integrity](https://www.frontiersin.org/about/research-integrity)
  * [Research Topics](https://www.frontiersin.org/about/research-topics)


  * Services
  * [Societies](https://publishingpartnerships.frontiersin.org/)
  * [National consortia](https://www.frontiersin.org/open-access-agreements/consortia)
  * [Institutional partnerships](https://www.frontiersin.org/about/open-access-agreements)
  * [Collaborators](https://www.frontiersin.org/about/collaborators)


  * More from Frontiers
  * [Frontiers Forum](https://forum.frontiersin.org/)
  * [Frontiers Planet Prize](https://www.frontiersplanetprize.org/)
  * [Press office](https://pressoffice.frontiersin.org/)
  * [Sustainability](https://www.frontiersin.orgabout/sustainability)
  * [Career opportunities](https://careers.frontiersin.org/)
  * [Contact us](https://www.frontiersin.org/about/contact)



[All journals](https://www.frontiersin.org/journals)[All articles](https://www.frontiersin.org/articles) [Submit your research](https://www.frontiersin.org/submission/submit?domainid=1&fieldid=62&specialtyid=0&entitytype=2&entityid=176)

[![]() Frontiers in Pharmacology](//www.frontiersin.org/journals/pharmacology)

Sections 

Sections 

  * [Cardiovascular and Smooth Muscle Pharmacology](/journals/pharmacology/sections/cardiovascular-and-smooth-muscle-pharmacology)
  * [Drug Metabolism and Transport](/journals/pharmacology/sections/drug-metabolism-and-transport)
  * [Drugs Outcomes Research and Policies](/journals/pharmacology/sections/drugs-outcomes-research-and-policies)
  * [ELSI in Science and Genetics](/journals/pharmacology/sections/elsi-in-science-and-genetics)
  * [Ethnopharmacology](/journals/pharmacology/sections/ethnopharmacology)
  * [Experimental Pharmacology and Drug Discovery](/journals/pharmacology/sections/experimental-pharmacology-and-drug-discovery)
  * [Gastrointestinal and Hepatic Pharmacology](/journals/pharmacology/sections/gastrointestinal-and-hepatic-pharmacology)
  * [Inflammation Pharmacology](/journals/pharmacology/sections/inflammation-pharmacology)
  * [Integrative and Regenerative Pharmacology](/journals/pharmacology/sections/integrative-and-regenerative-pharmacology)
  * [Neuropharmacology](/journals/pharmacology/sections/neuropharmacology)
  * [Obstetric and Pediatric Pharmacology](/journals/pharmacology/sections/obstetric-and-pediatric-pharmacology)
  * [Pharmacoepidemiology](/journals/pharmacology/sections/pharmacoepidemiology)
  * [Pharmacogenetics and Pharmacogenomics](/journals/pharmacology/sections/pharmacogenetics-and-pharmacogenomics)
  * [Pharmacology of Anti-Cancer Drugs](/journals/pharmacology/sections/pharmacology-of-anti-cancer-drugs)
  * [Pharmacology of Infectious Diseases](/journals/pharmacology/sections/pharmacology-of-infectious-diseases)
  * [Pharmacology of Ion Channels and Channelopathies](/journals/pharmacology/sections/pharmacology-of-ion-channels-and-channelopathies)
  * [Predictive Toxicology](/journals/pharmacology/sections/predictive-toxicology)
  * [Renal Pharmacology](/journals/pharmacology/sections/renal-pharmacology)
  * [Respiratory Pharmacology](/journals/pharmacology/sections/respiratory-pharmacology)
  * [Translational Pharmacology](/journals/pharmacology/sections/translational-pharmacology)



[Articles](//www.frontiersin.org/journals/pharmacology/articles)[Research Topics](//www.frontiersin.org/journals/pharmacology/research-topics)[Editorial board](//www.frontiersin.org/journals/pharmacology/editors)

About journal 

About journal 

  * Scope
  * [Field chief editors](https://www.frontiersin.org/journals/pharmacology/about#about-editors)
  * [Mission & scope](https://www.frontiersin.org/journals/pharmacology/about#about-scope)
  * [Facts](https://www.frontiersin.org/journals/pharmacology/about#about-facts)
  * [Journal sections](https://www.frontiersin.org/journals/pharmacology/about#about-submission)
  * [Open access statement](https://www.frontiersin.org/journals/pharmacology/about#about-open)
  * [Copyright statement](https://www.frontiersin.org/journals/pharmacology/about#copyright-statement)
  * [Quality](https://www.frontiersin.org/journals/pharmacology/about#about-quality)


  * For authors
  * [Why submit?](https://www.frontiersin.org/journals/pharmacology/for-authors/why-submit)
  * [Article types](https://www.frontiersin.org/journals/pharmacology/for-authors/article-types)
  * [Author guidelines](https://www.frontiersin.org/journals/pharmacology/for-authors/author-guidelines)
  * [Editor guidelines](https://www.frontiersin.org/journals/pharmacology/for-authors/editor-guidelines)
  * [Publishing fees](https://www.frontiersin.org/journals/pharmacology/for-authors/publishing-fees)
  * [Submission checklist](https://www.frontiersin.org/journals/pharmacology/for-authors/submission-checklist)
  * [Contact editorial office](https://www.frontiersin.org/journals/pharmacology/for-authors/contact-editorial-office)



[ ](//www.frontiersin.org/)

[![]() Frontiers in Pharmacology](//www.frontiersin.org/journals/pharmacology)

Sections 

Sections 

  * [Cardiovascular and Smooth Muscle Pharmacology](/journals/pharmacology/sections/cardiovascular-and-smooth-muscle-pharmacology)
  * [Drug Metabolism and Transport](/journals/pharmacology/sections/drug-metabolism-and-transport)
  * [Drugs Outcomes Research and Policies](/journals/pharmacology/sections/drugs-outcomes-research-and-policies)
  * [ELSI in Science and Genetics](/journals/pharmacology/sections/elsi-in-science-and-genetics)
  * [Ethnopharmacology](/journals/pharmacology/sections/ethnopharmacology)
  * [Experimental Pharmacology and Drug Discovery](/journals/pharmacology/sections/experimental-pharmacology-and-drug-discovery)
  * [Gastrointestinal and Hepatic Pharmacology](/journals/pharmacology/sections/gastrointestinal-and-hepatic-pharmacology)
  * [Inflammation Pharmacology](/journals/pharmacology/sections/inflammation-pharmacology)
  * [Integrative and Regenerative Pharmacology](/journals/pharmacology/sections/integrative-and-regenerative-pharmacology)
  * [Neuropharmacology](/journals/pharmacology/sections/neuropharmacology)
  * [Obstetric and Pediatric Pharmacology](/journals/pharmacology/sections/obstetric-and-pediatric-pharmacology)
  * [Pharmacoepidemiology](/journals/pharmacology/sections/pharmacoepidemiology)
  * [Pharmacogenetics and Pharmacogenomics](/journals/pharmacology/sections/pharmacogenetics-and-pharmacogenomics)
  * [Pharmacology of Anti-Cancer Drugs](/journals/pharmacology/sections/pharmacology-of-anti-cancer-drugs)
  * [Pharmacology of Infectious Diseases](/journals/pharmacology/sections/pharmacology-of-infectious-diseases)
  * [Pharmacology of Ion Channels and Channelopathies](/journals/pharmacology/sections/pharmacology-of-ion-channels-and-channelopathies)
  * [Predictive Toxicology](/journals/pharmacology/sections/predictive-toxicology)
  * [Renal Pharmacology](/journals/pharmacology/sections/renal-pharmacology)
  * [Respiratory Pharmacology](/journals/pharmacology/sections/respiratory-pharmacology)
  * [Translational Pharmacology](/journals/pharmacology/sections/translational-pharmacology)



[Articles](//www.frontiersin.org/journals/pharmacology/articles)[Research Topics](//www.frontiersin.org/journals/pharmacology/research-topics)[Editorial board](//www.frontiersin.org/journals/pharmacology/editors)

About journal 

About journal 

  * Scope
  * [Field chief editors](https://www.frontiersin.org/journals/pharmacology/about#about-editors)
  * [Mission & scope](https://www.frontiersin.org/journals/pharmacology/about#about-scope)
  * [Facts](https://www.frontiersin.org/journals/pharmacology/about#about-facts)
  * [Journal sections](https://www.frontiersin.org/journals/pharmacology/about#about-submission)
  * [Open access statement](https://www.frontiersin.org/journals/pharmacology/about#about-open)
  * [Copyright statement](https://www.frontiersin.org/journals/pharmacology/about#copyright-statement)
  * [Quality](https://www.frontiersin.org/journals/pharmacology/about#about-quality)


  * For authors
  * [Why submit?](https://www.frontiersin.org/journals/pharmacology/for-authors/why-submit)
  * [Article types](https://www.frontiersin.org/journals/pharmacology/for-authors/article-types)
  * [Author guidelines](https://www.frontiersin.org/journals/pharmacology/for-authors/author-guidelines)
  * [Editor guidelines](https://www.frontiersin.org/journals/pharmacology/for-authors/editor-guidelines)
  * [Publishing fees](https://www.frontiersin.org/journals/pharmacology/for-authors/publishing-fees)
  * [Submission checklist](https://www.frontiersin.org/journals/pharmacology/for-authors/submission-checklist)
  * [Contact editorial office](https://www.frontiersin.org/journals/pharmacology/for-authors/contact-editorial-office)



[Submit your research](https://www.frontiersin.org/submission/submit?domainid=1&fieldid=62&specialtyid=0&entitytype=2&entityid=176) [Search](/search)

REVIEW article 

Front. Pharmacol. , 24 April 2024

Sec. Cardiovascular and Smooth Muscle Pharmacology 

Volume 15 - 2024 |  [ https://doi.org/10.3389/fphar.2024.1396656 ](https://doi.org/10.3389/fphar.2024.1396656)

# Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

[![Tianyu Wang](https://loop.frontiersin.org/images/profile/2229982/74)Tianyu Wang](https://loop.frontiersin.org/people/2229982)1![Juncan Ding](https://loop.frontiersin.org/cdn/images/profile/default_32.jpg)Juncan Ding1![Xinyi Cheng](https://loop.frontiersin.org/cdn/images/profile/default_32.jpg)Xinyi Cheng1![Qiang Yang](https://loop.frontiersin.org/cdn/images/profile/default_32.jpg)Qiang Yang1![Pengfei Hu
](https://loop.frontiersin.org/cdn/images/profile/default_32.jpg)Pengfei Hu2*

  * 1Department of The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
  * 2Department of Cardiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China



Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of cardiovascular mortality and is increasingly prevalent in our population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can safely and effectively lower glucose levels while concurrently managing the full spectrum of ASCVD risk factors and improving patients' long-term prognosis. Several cardiovascular outcome trials (CVOTs) have been carried out to further investigate the cardiovascular benefits of GLP-1RAs. Analyzing data from CVOTs can provide insights into the pathophysiologic mechanisms by which GLP-1RAs are linked to ASCVD and define the use of GLP-1RAs in clinical practice. Here, we discussed various mechanisms hypothesized in previous animal and preclinical human studies, including blockade of the production of adhesion molecules and inflammatory factors, induction of endothelial cells' synthesis of nitric oxide, protection of mitochondrial function and restriction of oxidative stress, suppression of NOD-like receptor thermal protein domain associated protein three inflammasome, reduction of foam cell formation and macrophage inflammation, and amelioration of vascular smooth muscle cell dysfunction, to help explain the cardiovascular benefits of GLP-1RAs in CVOTs. This paper provides an overview of the clinical research, molecular processes, and possible therapeutic applications of GLP-1RAs in ASCVD, while also addressing current limitations in the literature and suggesting future research directions.

## 1 Introduction

Atherosclerotic cardiovascular disease (ASCVD) encompasses a range of conditions, comprising acute coronary syndrome (ACS), stable angina pectoris, coronary or other revascularization, transient ischemic attack, ischemic stroke, and peripheral vascular lesions (Bostrom et al., 2021). The disease process of atherosclerosis (AS) is intricate, involving the accumulation of AS-causing lipoproteins in endothelial cells and the formation of AS plaques due to extracellular matrix, vascular smooth muscle cells (VSMCs), immune cells, immunoglobulins, necrotic cellular debris, and neovascularization with intra-plaque hemorrhage (Libby et al., 2019). ASCVD accounted for over 17 million fatalities worldwide in 2015 (Belardo et al., 2022; Liu et al., 2022), underscoring its significant impact on individuals, their families, and social healthcare systems, and highlighting the urgent need for preventive and therapeutic measures for ASCVD (Lenharo, 2023). Preventing the progression of severe ASCVD is expected to reduce the occurrence of major adverse cardiovascular events (MACE) (Kalra et al., 2021).

Risk factors for ASCVD include hypertension, hyperglycemia, hyperlipidemia, smoking, and obesity (Chu et al., 2020). While progress has been made in reducing the incidence of ASCVD through smoking cessation, blood pressure and low-density lipoprotein (LDL) control, the global rise in type 2 diabetes mellitus (T2DM) poses a new challenge for the prevention and treatment of ASCVD (Wang et al., 2018). T2DM is a highly influential risk factor for the progression of ASCVD (Valanti et al., 2021). With the implementation of standard treatments for T2DM, including weight loss, glucose reduction, as well as antihypertensive and lipid-lowering therapies, patients with T2DM have had a notable decrease in both cardiovascular events and mortality. However, there is still much room for improvement, as cardiovascular issues remain a leading cause of mortality among patients with T2DM (Acosta et al., 2021). Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that acts as an insulin stimulator. It promotes the release of insulin from pancreatic β-cells in response to glucose while inhibiting glucagon secretion from pancreatic α-cells. Furthermore, GLP-1 slows stomach emptying and helps convey feelings of fullness in the central nervous system (Scheen, 2018; Tilinca et al., 2021). The GLP-1 receptor (GLP-1R) is widely distributed in the cardiovascular system. Multinational, multicenter prospective cardiovascular outcome trials (CVOTs) have verified that GLP-1R agonists (GLP-1RAs) provide cardiovascular benefits and reduce cardiovascular mortality independent of their glucose-lowering effects (Caruso et al., 2019).

This paper provides a comprehensive review of CVOTs investigating the use of GLP-1RAs in individuals with risk factors for or diagnosed with ASCVD, offering critical data from these CVOTs. In addition, this paper also make investigation into the direct relationship between GLP-1RAs and AS pathogenesis.

## 2 Methods

We searched PubMed and Web of Science for articles published between February 2004 and February 2024. We searched the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al., 2021). The search terms were "glucagon-like peptide-1", "glucagon-like peptide-1 receptor agonist", "beinaglutide", "dulaglutide", "exenatide", "semaglutide", "liraglutide", "type 2 diabetes mellitus", "atherosclerosis", "atherosclerotic cardiovascular disease", "coronary atherosclerosis", "stable angina", "unstable angina", "coronary revascularization", "cardiovascular outcome trials", "platelet activation", "blood glucose", "blood pressure, lipids", "macrophages", "inflammation" and "oxidative stress" alone or in combination. Inclusion and exclusion criteria were used in the selection of articles (Figure 1).

Figure 1

[ ![www.frontiersin.org](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-g001.jpg) ](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-g001.jpg)

**Figure 1**. PRISMA flow diagram of included studies.

### 2.1 Inclusion

• all types of ASCVD

• qualifying both _in vivo_ and _in vitro_ studies

### 2.2 Exclusion

• articles in a language other than English

• articles from before 2004

• no clearly defined effect of GLP-1RAs on ASCVD

• articles on GLP-1RAs for other related diseases but not ASCVD

## 3 GLP-1 and its receptors

Following food intake, particularly glucose and other carbs, neuroendocrine L cells in the distal ileum and colon biphasically produce GLP-1, a peptide of 30 amino acids (Trujillo et al., 2021). Upon release into the bloodstream, GLP-1 attaches to and activates a specific and widely expressed receptor, GLP-1R (Aroda, 2018). Endogenous GLP-1 has a short plasma half-life of roughly two to 3 minutes (Chen et al., 2022). Consequently, GLP-1RAs have emerged to extend the half-life by modifying GLP-1's structure and binding to GLP-1R in a glucose concentration-dependent manner to regulate blood glucose (Hall et al., 2018). Numerous clinical investigations have confirmed the hypoglycemic effectiveness of GLP-1RAs, which are categorized into short-acting and long-acting formulations. Short-acting GLP-1RAs, such as beinaglutide, lixisenatide, and exenatide, primarily reduce postprandial blood glucose and delay stomach emptying (Kaneto et al., 2021). In contrast, long-acting GLP-1RAs, including liraglutide, dulaglutide, semaglutide, and albiglutide, increase insulin secretion and decrease glucagon secretion, thus lowering fasting and postprandial blood glucose levels (Davies et al., 2018). GLP-1RAs have been demonstrated to offer significant cardiovascular benefits in addition to their glucose-lowering effects (Thomas et al., 2023). They prevent and stabilize ASCVD in both patients with and without T2DM through mechanisms that include not only glucose-lowering and weight-loss but also inhibition of inflammatory factors and adhesion molecules, suppression of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, induction of nitric oxide (NO) synthesis in endothelial cells, protection of mitochondrial function and inhibition of oxidative stress, reduction of macrophage inflammation and foam cell formation, and improvement of VSMC dysfunction (Sposito et al., 2018; Saraiva and Franco, 2021; Yang et al., 2021).

## 4 CVOTs of GLP-1RAs

The U.S. Food and Drug Administration published CVD risk evaluation guidelines for new drugs for T2DM in 2008 (Ussher and Drucker, 2023). GLP-1RAs have been demonstrated to offer significant cardiovascular benefits in addition to their glucose-lowering effects (Table 1). These studies were conducted to thoroughly examine the impact of the medication and placebo on cardiovascular outcomes in individuals with T2DM diagnosed with or having risk factors for CVD (Dardano et al., 2020). GLP-1RAs demonstrated superior glucose-lowering effects in CVOTs and significant effects on MACE risk reduction (Table 2), attracting considerable attention from cardiologists (Schubert et al., 2020; Martens et al., 2023).

Table 1

[ ![www.frontiersin.org](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-t001.jpg) ](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-t001.jpg)

**Table 1**. Effects of GLP-1RAs on change from baseline age (yr), BMI (kg/m2), HbA1c (%), LDL-C (mg/dL), SBP (mmHg) and eGFR (ml/min/1.73 m2) in people with or without T2DM.

Table 2

[ ![www.frontiersin.org](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-t002.jpg) ](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-t002.jpg)

**Table 2**. CVOTs evaluating GLP-1RAs in people with CVD (with or without T2DM).

### 4.1 Elixa

The earliest CVOTs on GLP-1RAs were the ELIXA study (Al Rifai et al., 2022). The investigation included 6068 patients with T2DM who had suffered an ACS within the past 6 months. Patients were randomly allocated to the lixisenatide or placebo groups, receiving treatment with either drug (maximum dose of 20 μg once/day, with a beginning dose of 10 μg for 2 weeks), and a median follow-up of 25 months. The probability of four-point MACE was not much higher in the lixisenatide group than in the placebo group (13.4% vs. 13.2%; hazard ratio [HR] = 1.02; 95% confidence interval [CI] 0.89-1.17; _p_ < 0.001 for non-inferiority; _p_ = 0.81 for superiority), based on the findings. Similarly, there were no significant differences in individual endpoint comparisons. However, an analysis of other secondary endpoints showed that treatment with lixisenatide led to a lower risk of developing new-onset massive albuminuria in patients with T2DM, slowed the progression of diabetic nephropathy in patients with massive albuminuria-associated T2DM, and demonstrated a positive impact on maintaining body weight (Pfeffer et al., 2015). ELIXA is the first reported randomized, double-blind, non-inferiority CVOTs of GLP-1RAs (Muskiet et al., 2018).

### 4.2 Leader

The 2016 LEADER trial was the first CVOT to report the cardioprotective benefits of GLP-1RAs, with liraglutide being the first GLP-1RA shown to have cardiovascular benefits (Buse et al., 2020). With a median follow-up of 3.8 years, 9,340 individuals with T2DM who had risk factors for or were diagnosed with CVD were included in the research. These patients were randomly assigned to the liraglutide (1.8 mg, once/day) or the placebo group. Patients in the liraglutide group were shown to have a 13% lower risk of three-point MACE compared to those in the placebo group (13.0% vs. 14.9%; HR = 0.87; 95% CI 0.78-0.97; _p_ < 0.001 for non-inferiority; _p_ = 0.01 for superiority). Interestingly, the randomized therapy for three-point MACE lasted 12-18 months until the Kaplan-Meier cumulative event curves started diverging, suggesting that the cardiovascular benefits of liraglutide may be mediated through its anti-AS effects (Verma et al., 2020). Secondary endpoint analyses showed that liraglutide significantly reduced the risk of cardiovascular death (4.7% vs. 6.0%; HR = 0.78; 95% CI 0.66-0.93; _p_ = 0.007) and all-cause mortality (8.2% vs. 9.6%; HR = 0.85; 95% CI 0.74-0.97; _p_ = 0.02) compared to placebo. Additionally, shown by other secondary endpoint analysis, there was a 22% decrease in the risk of new-onset nephropathy or exacerbation of nephropathy in the liraglutide group (5.7% vs. 7.2%; HR = 0.78; 95% CI 0.67-0.92; _p_ = 0.003) (Marso et al., 2016b; Mann et al., 2017). The LEADER study made liraglutide the second hypoglycemic agent after the sodium-glucose cotransporter-2 inhibitor (SGLT2i), empagliflozin, to demonstrate cardiovascular benefits in randomized clinical trials, which was a significant breakthrough and source of inspiration for cardiologists and researchers, marking a landmark in the field (Kristensen et al., 2019).

### 4.3 Sustain-6

The purpose of the trial was to determine whether semaglutide was not less safe for the cardiovascular system than a placebo in individuals with T2DM (Aroda et al., 2019). A total of 3297 T2DM patients aged 50 years or older were enrolled, with 83% having confirmed CVD, chronic kidney disease, or both. The participants were assigned to receive either semaglutide (0.5 or 1.0 mg once per week) or placebo at random, and were followed for a median duration of 104 weeks. The findings demonstrated that, in comparison to placebo, individuals receiving semaglutide had a noticeably decreased risk of three-point MACE (6.6% vs. 8.9%; HR = 0.74; 95% CI 0.58-0.95; _p_ < 0.001 for non-inferiority; _p_ = 0.02 for superiority), with a notable decrease in the risk of nonfatal stroke (1.6% vs. 2.7%; HR = 0.61; 95% CI 0.38-0.99; _p_ = 0.04) and a significant cardiovascular benefit. However, when compared to placebo, semaglutide did not lower the risk of cardiovascular death, nonfatal myocardial infarction (MI), or all-cause mortality. Furthermore, semaglutide dramatically decreased the risk of developing new or worsening nephropathy (3.8% vs. 6.1%; HR = 0.64; 95% CI 0.46-0.88; _p_ = 0.005) (Marso et al., 2016a). Currently, subcutaneous injection formulations of semaglutide have been submitted for marketing in several countries worldwide, and their clinical efficacy is promising. Although generally well tolerated, semaglutide was associated with an increased risk of retina-related issues (3.0% vs. 1.8%; HR = 1.76; 95% CI 1.11-2.78; _p_ = 0.02), necessitating careful consideration of its use in patients with comorbid retinopathy.

### 4.4 Exscel

The EXSCEL study, a randomized, double-blind, placebo-controlled clinical trial (Bethel et al., 2020), is the largest global clinical trial on GLP-1RAs. It was designed to evaluate the cardiovascular safety and efficacy of a weekly formulation of exenatide in patients with T2DM at all levels of CVD risk combined (Davis et al., 2022). The study enrolled 14,752 T2DM patients with HbA1C of 6.5%-10.0%, of whom 73.1% had a history of prior cardiovascular events, and 26.9% had no prior cardiovascular events. Participants were randomized to receive either exenatide (2 mg/week) or placebo on top of conventional therapy, with a median follow-up of 3.2 years. The primary composite endpoints of the study were cardiovascular death, nonfatal MI, and nonfatal stroke. The results showed that the risk of three-point MACE in the exenatide group was not significantly different from that in the placebo group (11.4% vs. 12.2%; HR = 0.91; 95% CI 0.83-1.00; _p_ < 0.001 for noninferiority; _p_ = 0.06 for superiority), implying that exenatide is safe in patients with T2DM but does not provide additional cardiovascular benefits. However, compared with placebo, exenatide improved several cardiovascular risk factors, expressing in overall least-squares mean difference such as a 0.53% decrease in HbA1C, a 1.27 kg decrease in body weight, and a 1.57 mmHg decrease in systolic blood pressure. There were no significant differences in the risk of severe hypoglycemia, acute pancreatitis, pancreatic cancer, and medullary thyroid carcinoma between the exenatide group and the placebo group (Holman et al., 2017).

### 4.5 Harmony

The HARMONY study of abirutide, published in 2018, enrolled 9,463 T2DM patients aged 40 years or older with confirmed ASCVD (coronary heart disease, cerebrovascular disease, or peripheral arterial disease) in 28 countries, excluding those with severe CKD (Green et al., 2018). Patients were randomized to receive either abirutide (30-50 mg/week) or placebo in addition to standard treatment, with a median follow-up of 1.6 years. Results showed a 22% reduction in the risk of three-point MACE in the abirutide group compared with the placebo group (7.0% vs. 9.0%; HR = 0.78; 95% CI 0.68-0.90; _p_ < 0.0001 for non-inferiority; _p_ = 0.0006 for superiority). Meanwhile, the Kaplan-Meier cumulative event curves for three-point MACE showed gradual separation only after 8 months of randomized treatment, suggesting that its cardiovascular protective effect was mainly achieved through anti-AS mechanisms. Despite the short follow-up period, the study adds more evidence to support the hypothesis that GLP-1RAs improve cardiovascular prognosis in patients with T2DM. There were no significant differences in the rates of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and other serious adverse events between the abirutide and placebo groups (Home, 2019). The drug was launched in Europe and the United States in 2014 but was later withdrawn from the global market in 2018 for economic reasons. Although the drug has been discontinued, the study provides essential information for understanding the GLP-1RAs class of hypoglycemic agents (Hernandez et al., 2018).

### 4.6 Rewind

The REWIND study of dulaglutide, published in 2019, stood out from previous CVOTs as the longest-follow-up CVOTs in the lowest CVD-risk and baseline glycated hemoglobin A1c (HbA1c) population (Webb et al., 2022). The research enrolled 9,901 T2DM patients aged 50 years or older with confirmed CVD or risk factors for CVD, with a baseline HbA1c of 7.2%. After a follow-up of 5.4 years, participants were assigned to either the placebo group or the dulaglutide (1.5 mg, once/week) group at random. The dulaglutide group showed a considerably reduced risk of three-point MACE than the placebo group (12.0% vs. 13.4%; HR = 0.88; 95% CI 0.79-0.99; _p_ = 0.026), and a notable decline in the risk of nonfatal stroke (2.7% vs. 3.5%; HR = 0.76; 95% CI 0.61-0.95; _p_ = 0.017). Stratified analyses revealed a more significant benefit for the primary composite endpoint in those aged ≥66 years, with a Body Mass Index (BMI) ≥ 32 kg/m2, and in the European or Asia-Pacific populations. In addition, when assessed within subgroups, the intervention HR for MACE was similar independent of the patient's history of CVD, indicating dulaglutide's efficacy in preventing both primary and secondary CVD (Gerstein et al., 2019). This favorable cardiovascular protective effect raises the questions of whether GLP-1RAs may be utilized in individuals with T2DM as a main preventive measure for CVD, which is expected to become a future research trend (Scott, 2020). However, as compared to other GLP-1RAs, dulaglutide showed a higher frequency of gastrointestinal side effects such as nausea and vomiting, and acute pancreatitis occurred in 12 users in the clinical study of this drug. While this may be related to individual patient factors, it still raises safety concerns that need further confirmation.

### 4.7 Pioneer 6

The PIONEER six study was the first global CVOT on oral GLP-1RAs (Husain et al., 2020). The study enrolled 3,183 T2DM patients with confirmed CVD or risk factors for CVD. They were randomized into two groups, receiving either semaglutide (14 mg, once/day) or placebo, with a median follow-up of 15.9 months. The study's findings failed to demonstrate that the oral semaglutide, as opposed to a placebo, substantially decreased the risk of MACE (3.8% vs. 4.8%; HR = 0.79; 95% CI 0.57-1.11; _p_ < 0.001 for non-inferiority; _p_ = 0.17 for superiority). There was also no significant difference in the risk of nonfatal MI and nonfatal stroke. However, in secondary endpoints, oral semaglutide did lower the risk of cardiovascular death (0.9% vs. 1.9%; HR = 0.49; 95% CI 0.27-0.92) and all-cause mortality (1.4% vs. 2.8%; HR = 0.51; 95% CI 0.31-0.84) in comparison to placebo. Furthermore, the effects of oral semaglutide on metabolic markers and safety showed that oral semaglutide reduced HbA1c, body weight, and systolic blood pressure. In terms of safety, it was consistent with previous GLP-1RAs' level of safety, with no additional safety concerns identified (Husain et al., 2019). Despite not demonstrating cardiovascular benefits, the study showed that oral semaglutide did not raise the risk of MACE, supporting its stability and safety for clinical use (Bain et al., 2019).

### 4.8 Amplitude-O

SGLT2i and GLP-1RAs have been shown to mechanistically complement each other in reducing cardiovascular events in patients with T2DM (Lam et al., 2022). The AMPLITUDE-O study was designed to evaluate the effect of SGLT2i on the efficacy and safety of efpeglenatide. Efpeglenatide is an animal-derived GLP-1RA based on the structure of exendin-4 with an elimination half-life of approximately 155 h (Tommerdahl et al., 2022). The study included 4,076 subjects with a baseline HbA1c of 8.9%, of whom 31.6% had an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, 89.5% had comorbid CVD, and 15.0% were on SGLT2i. Subjects were randomized in a 1:1:1 ratio to three groups. They received 4 mg or 6 mg efpeglenatide or placebo weekly subcutaneously, respectively, with a median follow-up of 1.81 years. The primary composite endpoints of the study were nonfatal MI, nonfatal stroke, and death from cardiovascular causes or unknown causes. Although a large proportion of patients in the AMPLITUDE-O trial were also treated with SGLT2i, efpeglenatide reduced the risk of three-point MACE regardless of SGLT2i treatment. The risk of three-point MACE was significantly reduced by 27% in the efpeglenatide group compared with the placebo group (7.0% vs. 9.2%; HR = 0.73; 95% CI 0.58-0.92; _p_ < 0.001 for non-inferiority; _p_ = 0.007 for superiority). There was a significant 35% reduction in the risk of three-point MACE in the efpeglenatide 6 mg group and also a trend toward a benefit in the risk of three-point MACE in the efpeglenatide 4 mg group. Both efpeglenatide doses showed a possible quantity-effect relationship on the primary composite endpoint. The secondary endpoint showed a 32% reduction in the composite renal outcome event in the efpeglenatide group compared with the placebo group (13.0% vs. 18.4%; HR = 0.68; 95% CI 0.57-0.79; _p_ < 0.001) (Gerstein et al., 2021). The graded benefit relationship between efpeglenatide dose and CVOTs suggests that using high doses of efpeglenatide or other GLP-1 RAs may maximize the cardiovascular and renal benefit profile (Gerstein et al., 2023).

### 4.9 Select

All of the above-mentioned CVOTs were conducted in patients with risk factors for or diagnosed CVD with comorbid T2DM. In contrast, the SELECT research was the first randomized, double-blind, multicenter, phase III clinical trial in patients with CVD who were not suffering from T2DM (Irfan, 2024). Prior to the SELECT study, there was no significant evidence of any hypoglycemic agents in reducing the risk of MACE or improving prognosis in individuals with CVD without T2DM (Nauck and Muller, 2023). The research recruited 17,604 overweight or obese individuals aged 45 years or older with confirmed CVD or high risk of CVD, excluding those with a HbA1c ≥ 6.5% or confirmed T2DM. Participants were randomized to receive either semaglutide or placebo in addition to their regular therapy. A weekly beginning dosage of 0.24 mg of semaglutide was given, with dose escalations (0.5, 1.0, 1.7, and 2.4 mg/week) every 4 weeks until reaching the target dosage of 2.4 mg at week 16. According to the results, individuals treated with semaglutide exhibited a 20% reduction in experiencing a three-point MACE than those in the placebo group (6.5% vs. 8.0%; HR = 0.80; 95% CI 0.72-0.90; _p_ < 0.001), and this reduction was consistent across subgroup analyses. Additionally, the semaglutide group had a 15% lower risk of cardiovascular death than the placebo group (2.5% vs. 3.0%; HR = 0.85; 95% CI 0.71-1.01; _p_ = 0.07), an 18% reduced risk in the heart failure composite endpoint (3.4% vs. 4.1%; HR = 0.82; 95% CI 0.71-0.96), and a 19% lower risk of all-cause mortality (4.3% vs. 5.2%; HR = 0.81; 95% CI 0.71-0.93) according to secondary endpoint findings (Lincoff et al., 2023). The results of the SELECT study are expected to influence the guidelines for treating ASCVD, potentially leading to a paradigm shift in clinical practice and a broader application of other GLP-1RAs (Lingvay et al., 2023).

## 5 Molecular mechanism of anti-AS by GLP-1RAs

### 5.1 Inhibition of the expression of inflammatory factors and adhesion molecules

Endothelial cells play a crucial role in the pathophysiological process of AS. GLP-1RAs exert protective effects on endothelial cell function by inhibiting endothelial cell expression of inflammatory factors and adhesion molecules, inducing NO synthesis in endothelial cells, protecting mitochondrial function, and inhibiting oxidative stress (Figure 2).

Figure 2

[ ![www.frontiersin.org](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-g002.jpg) ](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-g002.jpg)

**Figure 2**. Mechanism of GLP-1RAs in protecting endothelial cell function. High glucose leads to eNOS uncoupling, and high glucose stimulates the production of ROS from NOX expressed on endothelial cells through activation of PKC. ROS lead to mitochondrial dysfunction, increase the production of NF-κB, and mediate oxidative stress in endothelial cells. NF-κB increases the expression of inflammatory factors and adhesion molecules such as TNF-α, IL-6, ICAM-1, VCAM-1, E-selectin and P-selectin, and inhibits NO synthesis in endothelial cells, thereby inducing endothelial cell proliferation and migration. GLP-1RAs activate eNOS to inhibit the NF-κB signaling pathway and increase NO synthesis through the cAMP-dependent AMPK and PI3K/AKT signaling pathways. In addition, mitophagy plays a vital role in maintaining endothelial cell homeostasis, whereas excessive mitophagy after mitochondrial dysfunction increases ROS release instead. GLP-1RAs not only ameliorated mitochondrial dysfunction but also inhibited the recruitment of PINK1/Parkin, preventing excessive mitophagy. AKT, protein kinase B; AMPK, AMP-activated protein kinase; cAMP, cyclic adenosine monophosphate; ECs, endothelial cells; eNOS, endothelial-type nitric oxide synthase; GLP-1RAs, glucagon-like peptide-1 receptor agonists; ICAM-1, intercellular adhesion molecule-1; IL-6, interleukin-6; LC3, microtubule-associated protein 1A/1B-light chain 3; NF-κB, nuclear factor-κB; NO, nitric oxide; NOX, NAPDH oxidase; PI3K, phosphatidylinositol 3-kinase; PINK1, PTEN-induced putative kinase 1; PKA, protein kinase A; PKC, protein kinase C; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α; ub, ubiquitin; VCAM-1, vascular cell adhesion molecule-1.

An animal study showed that liraglutide attenuated intimal hyperplasia after coronary stent implantation and significantly lower levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), two pro-inflammatory factors and elevated IL-10, an anti-inflammatory factor, levels (Bruen et al., 2019; Berndt et al., 2021). In a meta-analysis incorporating data from SUSTAIN3 and PIONEER1, 2, and 5, semaglutide significantly reduced hypersensitive C-reactive protein levels (Rakipovski et al., 2018; Jensen J. K. et al., 2022). It is believed that inflammatory alterations in endothelial cells, caused by blood flow, occur concurrently with the development of AS. Endothelial cell activation leads to the expression of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin, which draw in lymphocytes and monocytes, attach to endothelial cells, and penetrate the artery, initiating an inflammatory response (Libby, 2021). In an _in vitro_ model, GLP-1RAs have been reported to downregulate these adhesion molecules' level in endothelial cells, which coincided with a decrease in pro-inflammatory indicators such as TNF-α, IL-6, nuclear factor-κB (NF-κB), and monocyte chemotactic protein-1 (MCP-1) (Zhang et al., 2020). In addition, GLP-1RAs block oxidized LDL (ox-LDL)-induced monocyte adhesion to endothelial cells via regulating the ERK5/KLF2 signaling pathway (Yue et al., 2019). By downregulating certain inflammatory factors and adhesion molecules in the artery wall, GLP-1RAs prevent the concentration of monocytes and macrophages, leading to inflammation inhibition in the endothelial cells and achieving an anti-AS effect. Given the importance of inflammation in the development of AS, the therapeutic concept of reducing inflammation as a strategy to prevent AS and its complications has gained increasing attention, with research on GLP-1RAs contributing significantly to advancing this concept (Luna-Marco et al., 2023).

### 5.2 Induction of NO synthesis in endothelial cells

Endothelial-type nitric oxide synthase (eNOS) has been reported to have cardioprotective functions (Helmstadter et al., 2020). In in vitro experiments, GLP-1RAs have been shown to bind to GLP-1R on endothelial cells, leading to activated eNOS, increased NO production, and inhibition of NF-κB activation, thereby protecting endothelial cells (Tang et al., 2018; Wu et al., 2021). Erdogdu et al. (Erdogdu et al., 2010) found that eNOS in exenatide-stimulated human coronary artery endothelial cells (hCAECs) is activated by phosphorylation through cyclic adenosine monophosphate (cAMP)-dependent AMPK and PI3K/AKT signaling pathways, resulting in a direct protective effect on endothelial cells. Exenatide also promotes hCAEC proliferation in a MAPK/ERK1/2-independent manner (Han et al., 2019). Similarly, Wei et al. (Wei et al., 2016) confirmed Erdogdu's report that exenatide stimulation of human umbilical vein endothelial cells (HUVECs) led to the phosphorylation of eNOS, inducing NO production, an effect that could be eliminated by GLP-1RAs inhibitors and by specific inhibitors of signaling pathways. Liraglutide enhances eNOS expression in aortic endothelial cells and increases NO production, exerting an anti-inflammatory effect in vascular endothelial cells (Durak and Turan, 2023). Also, liraglutide functions as a catalyst to promote endothelial cell migration and proliferation, directly affecting vascular endothelial repair and revascularization (Yue et al., 2019). In addition, eNOS is not only expressed in endothelial cells but also in cardiomyocytes (Xiao et al., 2020). Regulation of cardiac NO synthesis has been suggested as a common pathway to explain the benefits of multiple effective therapies for ASCVD (Aung et al., 2019).

### 5.3 Protection of mitochondrial function and inhibition of oxidative stress

Reactive Oxygen Species (ROS) are a class of oxidizing molecules with unstable electrons, such as superoxide anion, hydrogen peroxide, and hydroxyl radicals (Yan et al., 2023). While ROS facilitates the regulation of cellular signaling and gene expression at a certain level, excessive ROS causes oxidative stress, resulting in vascular endothelial dysfunction, LDL oxidation, and, ultimately, ASCVD (Yu et al., 2023). ROS are produced by various sources, including NAPDH oxidase 4 (NOX), mitochondrial electron transport chain, and eNOS uncoupling (Senoner and Dichtl, 2019). The enzyme complex NOX located in the cell membrane produces superoxide radicals from oxygen (Chen et al., 2023). Protein kinase C (PKC) can activate NOX and increase ROS production brought on by elevated glucose levels (Aimo et al., 2020). By preventing PKC-mediated activation of NOX, liraglutide decreased the generation of ROS in human aortic endothelial cells (Sivalingam et al., 2021). Mitochondria serve as the cellular powerhouses, generating adenosine triphosphate (ATP) through oxidative phosphorylation and participating in calcium regulation and apoptosis (Wang and Kang, 2020). Impairment of the mitochondrial respiratory chain or high proton motive force increases ROS production. In contrast, GLP-1RAs can attenuate oxidative stress, improve respiratory chain activity, increase ATP production, and delay the progression of AS by protecting mitochondrial function (Luna-Marco et al., 2023). The generation of ROS and the preservation of cellular homeostasis depend heavily on mitophagy, a process driven by the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) (Guan et al., 2023). Under conditions of cellular stress, the mitochondrial membrane potential decreases, and PINK1 is unable to enter the inner mitochondrial membrane. Instead, it accumulates in the outer membrane, recruiting Parkin to activate mitophagy (Bader and Winklhofer, 2020). A cytoplasmic ubiquitin ligase called parkin migrates to injured mitochondria and promotes ROS leakage, which leads to mitochondrial breakdown (Connelly et al., 2023). However, under pathological conditions, excessive mitophagy may be a double-edged sword, especially in endothelial cells undergoing AS, where it results in mitochondrial breakage and excessive ROS production. In HUVECs, liraglutide exerts its effects at an earlier stage of this pathway by impeding the recruitment of PINK1/Parkin, reducing the occurrence of excessive mitophagy, and decreasing ROS release (Vandemark et al., 2023). A mouse cardiomyocyte model of hypoxia _in vitro_ showed that exenatide treatment resulted in a decrease in mitochondrial generation of ROS in cells. In contrast, intracellular signaling related to the maintenance of mitochondrial integrity was upregulated in these cells (Lambadiari et al., 2018). In addition to fundamental studies, a short clinical experiment was conducted to evaluate the antioxidant benefits of GLP-1RAs. It showed that plasma eight-iso-prostaglandin F2α (8-iso-PGF2α) levels were reduced in individuals with T2DM after 26 weeks of weekly injections of dulaglutide, suggesting lower levels of oxidative stress (Chang et al., 2019). The studies indicate that GLP-1RAs have antioxidant properties by decreasing ROS generation, and the effects are partially independent of their glucose-lowering effects.

### 5.4 Inhibition of NLRP3 inflammasome

Macrophages are present throughout the development of AS, contributing to the formation of foam cells after phagocytosis of ox-LDL and further releasing inflammatory cytokines. GLP-1RAs have been reported to inhibit macrophage NLRP3 inflammasome, reducing macrophage inflammation and foam cell formation, highlighting GLP-1RAs' vital protective role in AS (Figure 3).

Figure 3

[ ![www.frontiersin.org](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-g003.jpg) ](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-g003.jpg)

**Figure 3**. Mechanism of GLP-1RAs in reducing macrophage inflammation and foam cell formation. Inflammatory factors such as M-CSF, TNF-α, IFN-γ, and IL-18 attract monocytes to migrate and infiltrate in the vasculature of AS, differentiate into M1 macrophages, and activate the NF-κB signaling pathway, which mediates the generation of ROS. M1 macrophages accumulate and phagocytose oxLDL to become foam cells. NF-κB promotes the release of more inflammatory factors from the macrophages and activates NLRP3 inflammasome. The NLRP3 inflammasome is a crucial component of the innate immune system, inducing the secretion of pro-inflammatory cytokines IL-1β/18, activating caspase-1 to promote GSDMD-mediated cellular pyroptosis. GLP-1RAs promote mitophagy in dysfunctional mitochondria and inhibit ROS production via the SIRT1/NOX4 signaling pathway, thereby inhibiting the activation of NLRP3 inflammasome. GLP-1RAs promote the transformation of M1 macrophages to M2 through inhibition of the CEBPβ/mTOR and MAPK signaling pathways and increase the proportion of M2 macrophages with anti-inflammatory functions. In addition, GLP-1RAs directly inhibits foam cell formation by downregulating ACAT1. ACAT1, acetyl-CoA acetyltransferase 1; AS, atherosclerosis; ASC, apoptosis-associated speck-like protein with a caspase recruitment domain; CEBPβ, CCAAT/enhancer-binding proteinβ; ERK, extracellular signal-regulated kinase; G-, Gram-negative; GLP-1RAs, glucagon-like peptide-1 receptor agonists; GSDMD, gasdermin D; IFN-γ, interferon-γ; IL-18, interleukin-18; IL-1β, interleukin-1β; JNK, c-Jun N-terminal kinase; LC3, microtubule-associated protein 1A/1B-light chain 3; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemotactic protein-1; M-CSF, macrophage colony-stimulating factor; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-κB; NLRP3, NOD-like receptor thermal protein domain associated protein 3; NOX4, NAPDH oxidase four; oxLDL, oxidized low-density lipoprotein; PINK1, PTEN-induced putative kinase 1; ROS, reactive oxygen species; SIRT1, sirtuin 1; TNF-α, tumor necrosis factor-α; ub, ubiquitin.

NLRP3 is a 118 kDa cytoplasmic pattern recognition receptor (PRR) protein found in a wide type of cells (Ye et al., 2023; Zhang et al., 2023). The cytoplasmic multiprotein signaling complexes, known as NLRP3 inflammasomes, are formed when NLRP3 is activated (Wang and Hauenstein, 2020). The caspase-1, apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), and the NLRP3 protein make up the NLRP3 inflammasome (Li et al., 2020a). Hyperactivation of the NLRP3 inflammasome is linked to the pathogenic progression of ASCVD (Abbate et al., 2020). Duewell et al. (Tanase et al., 2023) demonstrated the NLRP3 inflammasome's critical role in AS by using LDL receptor (LDLR)-deficient mice with NLRP3−/−, ASC−/−, and IL-1α/β−/− bone marrow. After 8 weeks of high-fat diets, mice showed reduced levels of IL-18, caspase-1/11 in the bone marrow, and significantly reduced AS plaques (Liaqat et al., 2020), providing the first solid evidence that NLRP3 inflammasome promotes AS development. Following this observation, Shi et al. (Xu et al., 2022) found upregulated levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in carotid atherosclerotic plaques from patients undergoing carotid endarterectomy, with unstable plaques expressing higher levels of these compounds as opposed to stable plaques. In contrast, inhibition of the NLRP3 signaling pathway by siRNA interference suppressed pro-inflammatory cytokines in high-fat diet-fed ApoE−/− mice (Jin et al., 2022). Given the critical role of the NLRP3 inflammasome in the onset of AS, using NLRP3 inflammasome as therapeutic targets has become a new hotspot in anti-AS drug research (Martinez et al., 2018). Additionally, GLP-1RAs may be related to the NLRP3 inflammasome. Liraglutide, for example, was shown to reverse sirtuin 1 (SIRT1), NOX4 levels, and ROS generation by modulating TNF-α and SIRT1/NOX4/ROS pathway in the hypoxia-induced H9c2 cells, thereby suppressing the NLRP3 inflammasome-dependent cellular pyroptosis. In contrast, the SIRT1 inhibitor EX 527 nullified the beneficial impact of liraglutide (Chen et al., 2018; Luo et al., 2019). Song et al. (Song et al., 2022) also demonstrated the impact of liraglutide in attenuating central nervous inflammation and demyelination was also associated with the modulation of the NLRP3 pathway. In addition, GLP-1RAs inhibit NLRP3 inflammasome both directly and indirectly. Shao et al. (Wang W. et al., 2023) found that GLP-1RAs mitigate liver damage caused by oxidative stress by promoting the mitophagy pathway and suppressing the NLRP3 inflammasome, an effect that can be eliminated by PINK1 siRNA.

### 5.5 Reduction of macrophage inflammation and foam cell formation

Under pathological conditions, macrophages participate in the process of inflammation, which drives the progression of AS (Linton et al., 2019). GLP-1RAs reduce macrophage infiltration and inhibit macrophage-derived inflammatory factors (Yang et al., 2021). Animal studies have shown that semaglutide slowed plaque progression in rabbits with AS compared to the placebo group, and the histologic examination showed decreased macrophage infiltration despite there being lower LDL levels in the control group (Pan et al., 2023). Similar results were observed in ApoE−/− mice treated with liraglutide (Jensen D. M. et al., 2022). An _in vitro_ study has demonstrated that treatment with liraglutide reduced MCP-1 levels, and macrophage TNF-α and IL-1β secretion in AS plaques and peripheral blood macrophages from patients with human carotid endarterectomy (Zheng et al., 2019). In addition, GLP-1RAs promote macrophage polarization toward M2, decrease the number of pro-inflammatory macrophages, and attenuate AS plaque load in the aortic root of ApoE−/− mice by affecting the CCAAT/enhancer-binding protein β, the MAPK and NF-κB signaling pathways (Li et al., 2020b). A clinical study conducted by Yang et al. (Yang et al., 2021) further demonstrated a reduction in the overall count of macrophages, an elevation in the percentage of M2 macrophages in the peripheral blood, and higher cell surface GLP-1R expression among individuals suffering from coronary artery disease by contrast with the controls. The increased percentage of M2 macrophages with anti-inflammatory and enhanced function decreased harmful alterations to the artery wall and promoted the stabilization of AS lesions (Hou et al., 2023). Thus, given the methods mentioned above, GLP-1RAs may prevent inflammation linked with macrophages. Foam cells, primarily derived from macrophages and VSMCs, constitute an essential component of AS plaques (Shah, 2019). Tashiro et al. (Tashiro et al., 2014) demonstrated that liraglutide inhibits the phenotypic conversion of VSMCs to macrophages, decreasing the generation of foam cells as well as the plaque area, and ultimately retarding the growth rate of AS plaques. A subsequent animal study revealed that liraglutide could inhibit foam cell formation by downregulating acetyl-CoA acetyltransferase 1 (ACAT1) (Qin and Song, 2022). This aligns with the findings of earlier research and fully demonstrates the direct inhibitory effect of GLP-1RAs on AS plaque formation.

### 5.6 Improvement of VSMC dysfunction

VSMC dysfunction is defined as abnormal proliferation, migration, senescence, apoptosis, necrosis, and phenotypic transformation (Zhu et al., 2019; Wang Q. et al., 2023), leading to aggravated vascular damage and accelerated progression of AS. Aberrant VSMC proliferation and migration promote the development of necrotic cores and the thickness of AS plaques (Miano et al., 2021). Here, we will discuss the role of GLP-1RAs in improving VSMC dysfunction (Figure 4).

Figure 4

[ ![www.frontiersin.org](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-g004.jpg) ](https://www.frontiersin.org/files/Articles/1396656/fphar-15-1396656-HTML/image_m/fphar-15-1396656-g004.jpg)

**Figure 4**. Mechanism of GLP-1RAs in improving VSMC dysfunction. AngII promotes ROS production in VSMCs and activates the NF-κB signaling pathway. AGEs activate NOX expressed on endothelial cells to produce ROS. ROS leads to mitochondrial dysfunction, inducing phenotype switching and premature senescence of VSMCs. GLP-1RAs inhibit the activation of Rac1 via the cAMP/PKA pathway, thereby resisting Ang II-induced ROS production and corresponding VSMC senescence. In addition, GLP-1RAs inhibit VSMC proliferation and migration by suppressing inflammatory signaling pathways such as NF-κB, ERK1/2, and PI3K/AKT. Activation of AMPK by APN inhibits the ERK1/2 and PI3K/AKT signaling pathways and attenuated mitochondrial dysfunction. GLP-1RAs increases the expression of APN in VSMCs. AGEs, advanced glycation end products; AKT, protein kinase B; AMPK, AMP-activated protein kinase; AngII, angiotensin II; APN, adiponectin; cAMP, cyclic adenosine monophosphate; ERK, extracellular signal-regulated kinase; GLP-1RAs, glucagon-like peptide-1 receptor agonists; MMPs, matrix metalloproteinases; NF-κB, nuclear factor-κB; NOX, NAPDH oxidase; PI3K, phosphatidylinositol 3-kinase; PKA, protein kinase A; Rac1, Ras-related C3 botulinum toxin substrate 1; ROS, reactive oxygen species; VSMCs, vascular smooth muscle cells.

Liraglutide was reported by Shi et al. (Zhou et al., 2023) to inhibit high-glucose-induced aberrant proliferation and migration of VSMCs through the ERK1/2 and PI3K/AKT signaling pathways (Allahverdian et al., 2018). While impaired VSMC autophagy accelerates stress-induced early senescence of VSMCs, activated autophagy helps VSMCs withstand toxic damage and support cell survival (Grootaert et al., 2018). Therefore, well-functioning VSMCs are essential to protect the vessel wall from AS. Numerous factors, including DNA damage, telomere shortening, oxidative stress, and mitochondrial dysfunction, may cause VSMC senescence (Chi et al., 2019; Shi et al., 2020). As a result of senescent cells' diminished capacity for proliferation, the fibrous cap VSMC content decreases, which disrupts repair after plaque rupture and promotes plaque instability (Durham et al., 2018). Senescence is a stress-adapted state in which VSMCs stop proliferating, undergoing significant morphological and metabolic changes while remaining alive. The cells choose to die when the harmful effects become too intense or too long-lasting (Bonetti et al., 2021). Exenatide has been shown to inhibit the activation of Ras-related C3 botulinum toxin substrate 1(Rac1) via the cAMP/PKA pathway, thereby resisting the generation of superoxide and subsequent VSMC aging induced by Angiotensin II (Ang II) (Berndt et al., 2021). The quiescent contractile and differentiable phenotypes of VSMC give way to the activated synthetic and dedifferentiated phenotypes during the phenotypic shift (Ashraf and Al Haj Zen, 2021). In rat coronary VSMCs, liraglutide blocks advanced glycation end products (AGEs)-induced phenotypic transformation via suppressing the NF-κB signaling pathway and activating the cAMP/PKA signaling pathway (Di et al., 2019). In addition, exenatide regulates mitochondrial dynamics by promoting VSMC adiponectin (APN) expression and attenuates mitochondrial dysfunction, thereby inhibiting VSMC dedifferentiation (Fan et al., 2020). Therefore, GLP-1RAs can reverse vascular remodeling and delay VSMC senescence, and investigating the molecular pathways behind VSMC dysfunction might provide evidence for developing novel approaches and finding therapeutic targets for managing ASCVD (Khat and Husain, 2018).

## 6 Conclusion

Clinical trials and mechanistic studies have demonstrated that GLP-1RAs offer favorable cardiovascular benefits independent of their known effects on glucose metabolism. These benefits may directly improve endothelial, VSMC, and immune cell function (Iorga et al., 2020). However, further investigation is required to ascertain whether this mechanism of cardiovascular protection is influenced by the activation of GLP-1R in the local area or by the cumulative peripheral effects that indirectly enhance vascular function. Additionally, the selection of GLP-1RAs for particular patients should take into account the structural variations amongst various GLP-1RAs since these variations may result in distinct clinical presentations. Subsequent clinical studies should explore how GLP-1RAs work in concert with the current standard care for ASCVD. In summary, continuously improving the molecular mechanism of GLP-1RAs in treating ASCVD will provide valuable insights for treating ASCVD.

## Author contributions

TW: Writing-original draft. JD: Writing-original draft. XC: Writing-original draft. QY: Writing-review and editing. PH: Writing-review and editing.

## Funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

## Acknowledgments

In the process of writing this paper, I would like to thank my family for their support and encouragement for me to persist in completing this article.

## Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

## Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

## References

Abbate, A., Toldo, S., Marchetti, C., Kron, J., Van Tassell, B. W., and Dinarello, C. A. (2020). Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease. _Circulation Res._ 126 (9), 1260-1280\. doi:10.1161/CIRCRESAHA.120.315937

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32324502/) | [CrossRef Full Text](https://doi.org/10.1161/CIRCRESAHA.120.315937) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Interleukin-1+and+the+inflammasome+as+therapeutic+targets+in+cardiovascular+disease&btnG=)

Acosta, S., Johansson, A., and Drake, I. (2021). Diet and lifestyle factors and risk of atherosclerotic cardiovascular disease-A prospective cohort study. _Nutrients_ 13 (11), 3822. doi:10.3390/nu13113822

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34836078/) | [CrossRef Full Text](https://doi.org/10.3390/nu13113822) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Diet+and+lifestyle+factors+and+risk+of+atherosclerotic+cardiovascular+disease-A+prospective+cohort+study&btnG=)

Aimo, A., Castiglione, V., Borrelli, C., Saccaro, L. F., Franzini, M., Masi, S., et al. (2020). Oxidative stress and inflammation in the evolution of heart failure: from pathophysiology to therapeutic strategies. _Eur. J. Prev. Cardiol._ 27 (5), 494-510\. doi:10.1177/2047487319870344

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31412712/) | [CrossRef Full Text](https://doi.org/10.1177/2047487319870344) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Oxidative+stress+and+inflammation+in+the+evolution+of+heart+failure:+from+pathophysiology+to+therapeutic+strategies&btnG=)

Allahverdian, S., Chaabane, C., Boukais, K., Francis, G. A., and Bochaton-Piallat, M.-L. (2018). Smooth muscle cell fate and plasticity in atherosclerosis. _Cardiovasc. Res._ 114 (4), 540-550\. doi:10.1093/cvr/cvy022

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29385543/) | [CrossRef Full Text](https://doi.org/10.1093/cvr/cvy022) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Smooth+muscle+cell+fate+and+plasticity+in+atherosclerosis&btnG=)

Al Rifai, M., Vaughan, E. M., Abushamat, L. A., Lee, M., Ramsey, D. J., Gupta, K., et al. (2022). Correlates of glucagon-like peptide-1 receptor agonist use among patients with atherosclerotic cardiovascular disease and type 2 diabetes mellitus (from the department of veterans affairs). _Am. J. Cardiol._ 172, 7-10\. doi:10.1016/j.amjcard.2022.02.013

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35305783/) | [CrossRef Full Text](https://doi.org/10.1016/j.amjcard.2022.02.013) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Correlates+of+glucagon-like+peptide-1+receptor+agonist+use+among+patients+with+atherosclerotic+cardiovascular+disease+and+type+2+diabetes+mellitus+\(from+the+department+of+veterans+affairs\)&btnG=)

Aroda, V. R. (2018). A review of GLP-1 receptor agonists: evolution and advancement, through the lens of randomised controlled trials. _Diabetes, Obes. Metabolism_ 20 (Suppl. 1), 22-33\. doi:10.1111/dom.13162

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29364586/) | [CrossRef Full Text](https://doi.org/10.1111/dom.13162) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=A+review+of+GLP-1+receptor+agonists:+evolution+and+advancement,+through+the+lens+of+randomised+controlled+trials&btnG=)

Aroda, V. R., Ahmann, A., Cariou, B., Chow, F., Davies, M. J., Jodar, E., et al. (2019). Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: insights from the SUSTAIN 1-7 trials. _Diabetes and Metabolism_ 45 (5), 409-418\. doi:10.1016/j.diabet.2018.12.001

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30615985/) | [CrossRef Full Text](https://doi.org/10.1016/j.diabet.2018.12.001) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Comparative+efficacy,+safety,+and+cardiovascular+outcomes+with+once-weekly+subcutaneous+semaglutide+in+the+treatment+of+type+2+diabetes:+insights+from+the+SUSTAIN+1-7+trials&btnG=)

Ashraf, J. V., and Al Haj Zen, A. (2021). Role of vascular smooth muscle cell phenotype switching in arteriogenesis. _Int. J. Mol. Sci._ 22 (19), 10585. doi:10.3390/ijms221910585

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34638923/) | [CrossRef Full Text](https://doi.org/10.3390/ijms221910585) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Role+of+vascular+smooth+muscle+cell+phenotype+switching+in+arteriogenesis&btnG=)

Aung, M. M., Slade, K., Freeman, L. A. R., Kos, K., Whatmore, J. L., Shore, A. C., et al. (2019). Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes. _Diabetologia_ 62 (9), 1701-1711\. doi:10.1007/s00125-019-4918-x

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31203378/) | [CrossRef Full Text](https://doi.org/10.1007/s00125-019-4918-x) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Locally+delivered+GLP-1+analogues+liraglutide+and+exenatide+enhance+microvascular+perfusion+in+individuals+with+and+without+type+2+diabetes&btnG=)

Bader, V., and Winklhofer, K. F. (2020). PINK1 and Parkin: team players in stress-induced mitophagy. _Biol. Chem._ 401 (6-7), 891-899\. doi:10.1515/hsz-2020-0135

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32297878/) | [CrossRef Full Text](https://doi.org/10.1515/hsz-2020-0135) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=PINK1+and+Parkin:+team+players+in+stress-induced+mitophagy&btnG=)

Bain, S. C., Mosenzon, O., Arechavaleta, R., Bogdański, P., Comlekci, A., Consoli, A., et al. (2019). Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: rationale, design and patient baseline characteristics for the PIONEER 6 trial. _Diabetes, Obes. Metabolism_ 21 (3), 499-508\. doi:10.1111/dom.13553

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30284349/) | [CrossRef Full Text](https://doi.org/10.1111/dom.13553) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Cardiovascular+safety+of+oral+semaglutide+in+patients+with+type+2+diabetes:+rationale,+design+and+patient+baseline+characteristics+for+the+PIONEER+6+trial&btnG=)

Belardo, D., Michos, E. D., Blankstein, R., Blumenthal, R. S., Ferdinand, K. C., Hall, K., et al. (2022). Practical, evidence-based approaches to nutritional modifications to reduce atherosclerotic cardiovascular disease: an American society for preventive cardiology clinical practice statement. _Am. J. Prev. Cardiol._ 10, 100323. doi:10.1016/j.ajpc.2022.100323

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35284849/) | [CrossRef Full Text](https://doi.org/10.1016/j.ajpc.2022.100323) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Practical,+evidence-based+approaches+to+nutritional+modifications+to+reduce+atherosclerotic+cardiovascular+disease:+an+American+society+for+preventive+cardiology+clinical+practice+statement&btnG=)

Berndt, J., Ooi, S. L., and Pak, S. C. (2021). What is the mechanism driving the reduction of cardiovascular events from glucagon-like peptide-1 receptor agonists? A mini review. _Mol. Basel, Switz._ 26 (16), 4822. doi:10.3390/molecules26164822

[CrossRef Full Text](https://doi.org/10.3390/molecules26164822) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=What+is+the+mechanism+driving+the+reduction+of+cardiovascular+events+from+glucagon-like+peptide-1+receptor+agonists?+A+mini+review&btnG=)

Bethel, M. A., Stevens, S. R., Buse, J. B., Choi, J., Gustavson, S. M., Iqbal, N., et al. (2020). Exploring the possible impact of unbalanced open-label drop-in of glucose-lowering medications on EXSCEL outcomes. _Circulation_ 141 (17), 1360-1370\. doi:10.1161/CIRCULATIONAHA.119.043353

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32098501/) | [CrossRef Full Text](https://doi.org/10.1161/CIRCULATIONAHA.119.043353) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Exploring+the+possible+impact+of+unbalanced+open-label+drop-in+of+glucose-lowering+medications+on+EXSCEL+outcomes&btnG=)

Bonetti, J., Corti, A., Lerouge, L., Pompella, A., and Gaucher, C. (2021). Phenotypic modulation of macrophages and vascular smooth muscle cells in atherosclerosis-nitro-redox interconnections. _Antioxidants Basel, Switz._ 10 (4), 516. doi:10.3390/antiox10040516

[CrossRef Full Text](https://doi.org/10.3390/antiox10040516) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Phenotypic+modulation+of+macrophages+and+vascular+smooth+muscle+cells+in+atherosclerosis-nitro-redox+interconnections&btnG=)

Bostrom, J. A., Mottel, B., and Heffron, S. P. (2021). Medical and surgical obesity treatments and atherosclerosis: mechanisms beyond typical risk factors. _Curr. Atheroscler. Rep._ 23 (10), 60. doi:10.1007/s11883-021-00961-0

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34351556/) | [CrossRef Full Text](https://doi.org/10.1007/s11883-021-00961-0) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Medical+and+surgical+obesity+treatments+and+atherosclerosis:+mechanisms+beyond+typical+risk+factors&btnG=)

Bruen, R., Curley, S., Kajani, S., Lynch, G., O'Reilly, M. E., Dillon, E. T., et al. (2019). Liraglutide attenuates preestablished atherosclerosis in apolipoprotein E-deficient mice via regulation of immune cell phenotypes and proinflammatory mediators. _J. Pharmacol. Exp. Ther._ 370 (3), 447-458\. doi:10.1124/jpet.119.258343

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31270216/) | [CrossRef Full Text](https://doi.org/10.1124/jpet.119.258343) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+attenuates+preestablished+atherosclerosis+in+apolipoprotein+E-deficient+mice+via+regulation+of+immune+cell+phenotypes+and+proinflammatory+mediators&btnG=)

Buse, J. B., Bain, S. C., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., et al. (2020). Cardiovascular risk reduction with liraglutide: an exploratory mediation analysis of the LEADER trial. _Diabetes Care_ 43 (7), 1546-1552\. doi:10.2337/dc19-2251

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32366578/) | [CrossRef Full Text](https://doi.org/10.2337/dc19-2251) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Cardiovascular+risk+reduction+with+liraglutide:+an+exploratory+mediation+analysis+of+the+LEADER+trial&btnG=)

Caruso, I., Cignarelli, A., and Giorgino, F. (2019). Heterogeneity and similarities in GLP-1 receptor agonist cardiovascular outcomes trials. _Trends Endocrinol. Metabolism TEM_ 30 (9), 578-589\. doi:10.1016/j.tem.2019.07.004

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31401015/) | [CrossRef Full Text](https://doi.org/10.1016/j.tem.2019.07.004) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Heterogeneity+and+similarities+in+GLP-1+receptor+agonist+cardiovascular+outcomes+trials&btnG=)

Chang, W., Zhu, F., Zheng, H., Zhou, Z., Miao, P., Zhao, L., et al. (2019). Glucagon-like peptide-1 receptor agonist dulaglutide prevents ox-LDL-induced adhesion of monocytes to human endothelial cells: an implication in the treatment of atherosclerosis. _Mol. Immunol._ 116, 73-79\. doi:10.1016/j.molimm.2019.09.021

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31630078/) | [CrossRef Full Text](https://doi.org/10.1016/j.molimm.2019.09.021) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Glucagon-like+peptide-1+receptor+agonist+dulaglutide+prevents+ox-LDL-induced+adhesion+of+monocytes+to+human+endothelial+cells:+an+implication+in+the+treatment+of+atherosclerosis&btnG=)

Chen, A., Chen, Z., Xia, Y., Lu, D., Yang, X., Sun, A., et al. (2018). Liraglutide attenuates NLRP3 inflammasome-dependent pyroptosis via regulating SIRT1/NOX4/ROS pathway in H9c2 cells. _Biochem. Biophysical Res. Commun._ 499 (2), 267-272\. doi:10.1016/j.bbrc.2018.03.142

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29571736/) | [CrossRef Full Text](https://doi.org/10.1016/j.bbrc.2018.03.142) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+attenuates+NLRP3+inflammasome-dependent+pyroptosis+via+regulating+SIRT1/NOX4/ROS+pathway+in+H9c2+cells&btnG=)

Chen, J., Mei, A., Wei, Y., Li, C., Qian, H., Min, X., et al. (2022). GLP-1 receptor agonist as a modulator of innate immunity. _Front. Immunol._ 13, 997578. doi:10.3389/fimmu.2022.997578

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36569936/) | [CrossRef Full Text](https://doi.org/10.3389/fimmu.2022.997578) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=GLP-1+receptor+agonist+as+a+modulator+of+innate+immunity&btnG=)

Chen, Y., Guo, X., Zeng, Y., Mo, X., Hong, S., He, H., et al. (2023). Oxidative stress induces mitochondrial iron overload and ferroptotic cell death. _Sci. Rep._ 13 (1), 15515. doi:10.1038/s41598-023-42760-4

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37726294/) | [CrossRef Full Text](https://doi.org/10.1038/s41598-023-42760-4) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Oxidative+stress+induces+mitochondrial+iron+overload+and+ferroptotic+cell+death&btnG=)

Chi, C., Li, D.-J., Jiang, Y.-J., Tong, J., Fu, H., Wu, Y.-H., et al. (2019). Vascular smooth muscle cell senescence and age-related diseases: state of the art. _Biochimica Biophysica Acta. Mol. Basis Dis._ 1865 (7), 1810-1821\. doi:10.1016/j.bbadis.2018.08.015

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31109451/) | [CrossRef Full Text](https://doi.org/10.1016/j.bbadis.2018.08.015) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Vascular+smooth+muscle+cell+senescence+and+age-related+diseases:+state+of+the+art&btnG=)

Chu, D. J., Al Rifai, M., Virani, S. S., Brawner, C. A., Nasir, K., and Al-Mallah, M. H. (2020). The relationship between cardiorespiratory fitness, cardiovascular risk factors and atherosclerosis. _Atherosclerosis_ 304, 44-52\. doi:10.1016/j.atherosclerosis.2020.04.019

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32590246/) | [CrossRef Full Text](https://doi.org/10.1016/j.atherosclerosis.2020.04.019) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+relationship+between+cardiorespiratory+fitness,+cardiovascular+risk+factors+and+atherosclerosis&btnG=)

Connelly, E. M., Frankel, K. S., and Shaw, G. S. (2023). Parkin and mitochondrial signalling. _Cell. Signal._ 106, 110631. doi:10.1016/j.cellsig.2023.110631

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36803775/) | [CrossRef Full Text](https://doi.org/10.1016/j.cellsig.2023.110631) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Parkin+and+mitochondrial+signalling&btnG=)

Dardano, A., Miccoli, R., Bianchi, C., Daniele, G., and Del Prato, S. (2020). Invited review. Series: implications of the recent CVOTs in type 2 diabetes: which patients for GLP-1RA or SGLT-2 inhibitor? _Diabetes Res. Clin. Pract._ 162, 108112. doi:10.1016/j.diabres.2020.108112

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32198123/) | [CrossRef Full Text](https://doi.org/10.1016/j.diabres.2020.108112) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Invited+review.+Series:+implications+of+the+recent+CVOTs+in+type+2+diabetes:+which+patients+for+GLP-1RA+or+SGLT-2+inhibitor?&btnG=)

Davies, M. J., D'Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., et al. (2018). Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American diabetes association (ada) and the European association for the study of diabetes (easd). _Diabetes Care_ 41 (12), 2669-2701\. doi:10.2337/dci18-0033

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30288571/) | [CrossRef Full Text](https://doi.org/10.2337/dci18-0033) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Management+of+hyperglycemia+in+type+2+diabetes,+2018.+A+consensus+report+by+the+American+diabetes+association+\(ada\)+and+the+European+association+for+the+study+of+diabetes+\(easd\)&btnG=)

Davis, T. M. E., Giczewska, A., Lokhnygina, Y., Mentz, R. J., Sattar, N., Holman, R. R., et al. (2022). Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the exenatide study of cardiovascular event lowering (EXSCEL). _Cardiovasc. Diabetol._ 21 (1), 116. doi:10.1186/s12933-022-01555-z

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35761271/) | [CrossRef Full Text](https://doi.org/10.1186/s12933-022-01555-z) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Effect+of+race+on+cardiometabolic+responses+to+once-weekly+exenatide:+insights+from+the+exenatide+study+of+cardiovascular+event+lowering+\(EXSCEL\)&btnG=)

Di, B., Li, H.-W., Li, W., and Hua, B. (2019). Liraglutide inhibited AGEs induced coronary smooth muscle cell phenotypic transition through inhibiting the NF-κB signal pathway. _Peptides_ 112, 125-132\. doi:10.1016/j.peptides.2018.11.008

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30513352/) | [CrossRef Full Text](https://doi.org/10.1016/j.peptides.2018.11.008) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+inhibited+AGEs+induced+coronary+smooth+muscle+cell+phenotypic+transition+through+inhibiting+the+NF-κB+signal+pathway&btnG=)

Durak, A., and Turan, B. (2023). Liraglutide provides cardioprotection through the recovery of mitochondrial dysfunction and oxidative stress in aging hearts. _J. Physiology Biochem._ 79 (2), 297-311\. doi:10.1007/s13105-022-00939-9

[CrossRef Full Text](https://doi.org/10.1007/s13105-022-00939-9) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+provides+cardioprotection+through+the+recovery+of+mitochondrial+dysfunction+and+oxidative+stress+in+aging+hearts&btnG=)

Durham, A. L., Speer, M. Y., Scatena, M., Giachelli, C. M., and Shanahan, C. M. (2018). Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness. _Cardiovasc. Res._ 114 (4), 590-600\. doi:10.1093/cvr/cvy010

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29514202/) | [CrossRef Full Text](https://doi.org/10.1093/cvr/cvy010) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Role+of+smooth+muscle+cells+in+vascular+calcification:+implications+in+atherosclerosis+and+arterial+stiffness&btnG=)

Erdogdu, O., Nathanson, D., Sjoholm, A., Nystrom, T., and Zhang, Q. (2010). Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor. _Mol. Cell. Endocrinol._ 325 (1-2), 26-35\. doi:10.1016/j.mce.2010.04.022

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/20452396/) | [CrossRef Full Text](https://doi.org/10.1016/j.mce.2010.04.022) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Exendin-4+stimulates+proliferation+of+human+coronary+artery+endothelial+cells+through+eNOS-PKA-+and+PI3K/Akt-dependent+pathways+and+requires+GLP-1+receptor&btnG=)

Fan, S.-H., Xiong, Q.-F., Wang, L., Zhang, L.-H., and Shi, Y.-W. (2020). Glucagon-like peptide 1 treatment reverses vascular remodelling by downregulating matrix metalloproteinase 1 expression through inhibition of the ERK1/2/NF-κB signalling pathway. _Mol. Cell. Endocrinol._ 518, 111005. doi:10.1016/j.mce.2020.111005

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32877753/) | [CrossRef Full Text](https://doi.org/10.1016/j.mce.2020.111005) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Glucagon-like+peptide+1+treatment+reverses+vascular+remodelling+by+downregulating+matrix+metalloproteinase+1+expression+through+inhibition+of+the+ERK1/2/NF-κB+signalling+pathway&btnG=)

Gerstein, H. C., Colhoun, H. M., Dagenais, G. R., Diaz, R., Lakshmanan, M., Pais, P., et al. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. _Lancet London, Engl._ 394 (10193), 121-130\. doi:10.1016/S0140-6736(19)31149-3

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31189511/) | [CrossRef Full Text](https://doi.org/10.1016/S0140-6736\(19\)31149-3) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Dulaglutide+and+cardiovascular+outcomes+in+type+2+diabetes+\(REWIND\):+a+double-blind,+randomised+placebo-controlled+trial&btnG=)

Gerstein, H. C., Li, Z., Ramasundarahettige, C., Baek, S., Branch, K. R. H., Del Prato, S., et al. (2023). Exploring the relationship between efpeglenatide dose and cardiovascular outcomes in type 2 diabetes: insights from the AMPLITUDE-O trial. _Circulation_ 147 (13), 1004-1013\. doi:10.1161/CIRCULATIONAHA.122.063716

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36802715/) | [CrossRef Full Text](https://doi.org/10.1161/CIRCULATIONAHA.122.063716) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Exploring+the+relationship+between+efpeglenatide+dose+and+cardiovascular+outcomes+in+type+2+diabetes:+insights+from+the+AMPLITUDE-O+trial&btnG=)

Gerstein, H. C., Sattar, N., Rosenstock, J., Ramasundarahettige, C., Pratley, R., Lopes, R. D., et al. (2021). Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. _N. Engl. J. Med._ 385 (10), 896-907\. doi:10.1056/NEJMoa2108269

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34215025/) | [CrossRef Full Text](https://doi.org/10.1056/NEJMoa2108269) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Cardiovascular+and+renal+outcomes+with+efpeglenatide+in+type+2+diabetes&btnG=)

Green, J. B., Hernandez, A. F., D'Agostino, R. B., Granger, C. B., Janmohamed, S., Jones, N. P., et al. (2018). Harmony Outcomes: a randomized, double-blind, placebo-controlled trial of the effect of albiglutide on major cardiovascular events in patients with type 2 diabetes mellitus-Rationale, design, and baseline characteristics. _Am. Heart J._ 203, 30-38\. doi:10.1016/j.ahj.2018.03.030

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30015066/) | [CrossRef Full Text](https://doi.org/10.1016/j.ahj.2018.03.030) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Harmony+Outcomes:+a+randomized,+double-blind,+placebo-controlled+trial+of+the+effect+of+albiglutide+on+major+cardiovascular+events+in+patients+with+type+2+diabetes+mellitus-Rationale,+design,+and+baseline+characteristics&btnG=)

Grootaert, M. O. J., Moulis, M., Roth, L., Martinet, W., Vindis, C., Bennett, M. R., et al. (2018). Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis. _Cardiovasc. Res._ 114 (4), 622-634\. doi:10.1093/cvr/cvy007

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29360955/) | [CrossRef Full Text](https://doi.org/10.1093/cvr/cvy007) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Vascular+smooth+muscle+cell+death,+autophagy+and+senescence+in+atherosclerosis&btnG=)

Guan, Z., Chen, J., Wang, L., Hao, M., Dong, X., Luo, T., et al. (2023). Nuanxinkang prevents the development of myocardial infarction-induced chronic heart failure by promoting PINK1/Parkin-mediated mitophagy. _Phytomedicine Int. J. Phytotherapy Phytopharm._ 108, 154494. doi:10.1016/j.phymed.2022.154494

[CrossRef Full Text](https://doi.org/10.1016/j.phymed.2022.154494) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Nuanxinkang+prevents+the+development+of+myocardial+infarction-induced+chronic+heart+failure+by+promoting+PINK1/Parkin-mediated+mitophagy&btnG=)

Hall, S., Isaacs, D., and Clements, J. N. (2018). Pharmacokinetics and clinical implications of semaglutide: a new glucagon-like peptide (GLP)-1 receptor agonist. _Clin. Pharmacokinet._ 57 (12), 1529-1538\. doi:10.1007/s40262-018-0668-z

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29915923/) | [CrossRef Full Text](https://doi.org/10.1007/s40262-018-0668-z) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Pharmacokinetics+and+clinical+implications+of+semaglutide:+a+new+glucagon-like+peptide+\(GLP\)-1+receptor+agonist&btnG=)

Han, F., Hou, N., Liu, Y., Huang, N., Pan, R., Zhang, X., et al. (2019). Liraglutide improves vascular dysfunction by regulating a cAMP-independent PKA-AMPK pathway in perivascular adipose tissue in obese mice. _Biomed. Pharmacother. = Biomedecine Pharmacother._ 120, 109537. doi:10.1016/j.biopha.2019.109537

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31605951/) | [CrossRef Full Text](https://doi.org/10.1016/j.biopha.2019.109537) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+improves+vascular+dysfunction+by+regulating+a+cAMP-independent+PKA-AMPK+pathway+in+perivascular+adipose+tissue+in+obese+mice&btnG=)

Helmstadter, J., Frenis, K., Filippou, K., Grill, A., Dib, M., Kalinovic, S., et al. (2020). Endothelial GLP-1 (Glucagon-Like peptide-1) receptor mediates cardiovascular protection by liraglutide in mice with experimental arterial hypertension. _Arteriosclerosis, Thrombosis, Vasc. Biol._ 40 (1), 145-158\. doi:10.1161/atv.0000615456.97862.30

[CrossRef Full Text](https://doi.org/10.1161/atv.0000615456.97862.30) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Endothelial+GLP-1+\(Glucagon-Like+peptide-1\)+receptor+mediates+cardiovascular+protection+by+liraglutide+in+mice+with+experimental+arterial+hypertension&btnG=)

Hernandez, A. F., Green, J. B., Janmohamed, S., D'Agostino, R. B., Granger, C. B., Jones, N. P., et al. (2018). Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. _Lancet London, Engl._ 392 (10157), 1519-1529\. doi:10.1016/S0140-6736(18)32261-X

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30291013/) | [CrossRef Full Text](https://doi.org/10.1016/S0140-6736\(18\)32261-X) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Albiglutide+and+cardiovascular+outcomes+in+patients+with+type+2+diabetes+and+cardiovascular+disease+\(Harmony+Outcomes\):+a+double-blind,+randomised+placebo-controlled+trial&btnG=)

Holman, R. R., Bethel, M. A., Mentz, R. J., Thompson, V. P., Lokhnygina, Y., Buse, J. B., et al. (2017). Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. _N. Engl. J. Med._ 377 (13), 1228-1239\. doi:10.1056/NEJMoa1612917

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/28910237/) | [CrossRef Full Text](https://doi.org/10.1056/NEJMoa1612917) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Effects+of+once-weekly+exenatide+on+cardiovascular+outcomes+in+type+2+diabetes&btnG=)

Home, P. (2019). Cardiovascular outcome trials of glucose-lowering medications: an update. _Diabetologia_ 62 (3), 357-369\. doi:10.1007/s00125-018-4801-1

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30607467/) | [CrossRef Full Text](https://doi.org/10.1007/s00125-018-4801-1) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Cardiovascular+outcome+trials+of+glucose-lowering+medications:+an+update&btnG=)

Hou, P., Fang, J., Liu, Z., Shi, Y., Agostini, M., Bernassola, F., et al. (2023). Macrophage polarization and metabolism in atherosclerosis. _Cell. Death Dis._ 14 (10), 691. doi:10.1038/s41419-023-06206-z

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37863894/) | [CrossRef Full Text](https://doi.org/10.1038/s41419-023-06206-z) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Macrophage+polarization+and+metabolism+in+atherosclerosis&btnG=)

Husain, M., Bain, S. C., Jeppesen, O. K., Lingvay, I., Sørrig, R., Treppendahl, M. B., et al. (2020). Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. _Diabetes, Obes. Metabolism_ 22 (3), 442-451\. doi:10.1111/dom.13955

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31903692/) | [CrossRef Full Text](https://doi.org/10.1111/dom.13955) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Semaglutide+\(SUSTAIN+and+PIONEER\)+reduces+cardiovascular+events+in+type+2+diabetes+across+varying+cardiovascular+risk&btnG=)

Husain, M., Birkenfeld, A. L., Donsmark, M., Dungan, K., Eliaschewitz, F. G., Franco, D. R., et al. (2019). Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. _N. Engl. J. Med._ 381 (9), 841-851\. doi:10.1056/NEJMoa1901118

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31185157/) | [CrossRef Full Text](https://doi.org/10.1056/NEJMoa1901118) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Oral+semaglutide+and+cardiovascular+outcomes+in+patients+with+type+2+diabetes&btnG=)

Iorga, R. A., Bacalbasa, N., Carsote, M., Bratu, O. G., Stanescu, A. M. A., Bungau, S., et al. (2020). Metabolic and cardiovascular benefits of GLP-1 agonists, besides the hypoglycemic effect (Review). _Exp. Ther. Med._ 20 (3), 2396-2400\. doi:10.3892/etm.2020.8714

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32765722/) | [CrossRef Full Text](https://doi.org/10.3892/etm.2020.8714) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Metabolic+and+cardiovascular+benefits+of+GLP-1+agonists,+besides+the+hypoglycemic+effect+\(Review\)&btnG=)

Irfan, H. (2024). Obesity, cardiovascular disease, and the promising role of semaglutide: insights from the SELECT trial. _Curr. Problems Cardiol._ 49 (1 Pt A), 102060. doi:10.1016/j.cpcardiol.2023.102060

[CrossRef Full Text](https://doi.org/10.1016/j.cpcardiol.2023.102060) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Obesity,+cardiovascular+disease,+and+the+promising+role+of+semaglutide:+insights+from+the+SELECT+trial&btnG=)

Jensen, D. M., Skovsted, G. F., Bonde, M. F. B., Bentzon, J. F., Rolin, B., Franck, G., et al. (2022a). Semaglutide treatment attenuates vessel remodelling in ApoE-/- mice following vascular injury and blood flow perturbation. _Atheroscler. Plus_ 49, 32-41\. doi:10.1016/j.athplu.2022.05.004

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36644202/) | [CrossRef Full Text](https://doi.org/10.1016/j.athplu.2022.05.004) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Semaglutide+treatment+attenuates+vessel+remodelling+in+ApoE-/-+mice+following+vascular+injury+and+blood+flow+perturbation&btnG=)

Jensen, J. K., Binderup, T., Grandjean, C. E., Bentsen, S., Ripa, R. S., and Kjaer, A. (2022b). Semaglutide reduces vascular inflammation investigated by PET in a rabbit model of advanced atherosclerosis. _Atherosclerosis_ 352, 88-95\. doi:10.1016/j.atherosclerosis.2022.03.032

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35400496/) | [CrossRef Full Text](https://doi.org/10.1016/j.atherosclerosis.2022.03.032) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Semaglutide+reduces+vascular+inflammation+investigated+by+PET+in+a+rabbit+model+of+advanced+atherosclerosis&btnG=)

Jin, Y., Liu, Y., Xu, L., Xu, J., Xiong, Y., Peng, Y., et al. (2022). Novel role for caspase 1 inhibitor VX765 in suppressing NLRP3 inflammasome assembly and atherosclerosis via promoting mitophagy and efferocytosis. _Cell. Death Dis._ 13 (5), 512. doi:10.1038/s41419-022-04966-8

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35641492/) | [CrossRef Full Text](https://doi.org/10.1038/s41419-022-04966-8) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Novel+role+for+caspase+1+inhibitor+VX765+in+suppressing+NLRP3+inflammasome+assembly+and+atherosclerosis+via+promoting+mitophagy+and+efferocytosis&btnG=)

Kalra, D., Vijayaraghavan, K., Sikand, G., Desai, N. R., Joshi, P. H., Mehta, A., et al. (2021). Prevention of atherosclerotic cardiovascular disease in south asians in the us: a clinical perspective from the national lipid association. _J. Clin. Lipidol._ 15 (3), 402-422\. doi:10.1016/j.jacl.2021.03.007

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/33846108/) | [CrossRef Full Text](https://doi.org/10.1016/j.jacl.2021.03.007) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Prevention+of+atherosclerotic+cardiovascular+disease+in+south+asians+in+the+us:+a+clinical+perspective+from+the+national+lipid+association&btnG=)

Kaneto, H., Kimura, T., Shimoda, M., Obata, A., Sanada, J., Fushimi, Y., et al. (2021). Favorable effects of GLP-1 receptor agonist against pancreatic β-cell glucose toxicity and the development of arteriosclerosis: "the earlier, the better" in therapy with incretin-based medicine. _Int. J. Mol. Sci._ 22 (15), 7917. doi:10.3390/ijms22157917

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34360682/) | [CrossRef Full Text](https://doi.org/10.3390/ijms22157917) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Favorable+effects+of+GLP-1+receptor+agonist+against+pancreatic+β-cell+glucose+toxicity+and+the+development+of+arteriosclerosis:+the+earlier,+the+better+in+therapy+with+incretin-based+medicine&btnG=)

Khat, D. Z., and Husain, M. (2018). Molecular mechanisms underlying the cardiovascular benefits of SGLT2i and GLP-1RA. _Curr. Diabetes Rep._ 18 (7), 45. doi:10.1007/s11892-018-1011-7

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29886514/) | [CrossRef Full Text](https://doi.org/10.1007/s11892-018-1011-7) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Molecular+mechanisms+underlying+the+cardiovascular+benefits+of+SGLT2i+and+GLP-1RA&btnG=)

Kristensen, S. L., Rørth, R., Jhund, P. S., Docherty, K. F., Sattar, N., Preiss, D., et al. (2019). Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. _Lancet. Diabetes and Endocrinol._ 7 (10), 776-785\. doi:10.1016/S2213-8587(19)30249-9

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31422062/) | [CrossRef Full Text](https://doi.org/10.1016/S2213-8587\(19\)30249-9) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Cardiovascular,+mortality,+and+kidney+outcomes+with+GLP-1+receptor+agonists+in+patients+with+type+2+diabetes:+a+systematic+review+and+meta-analysis+of+cardiovascular+outcome+trials&btnG=)

Lam, C. S. P., Ramasundarahettige, C., Branch, K. R. H., Sattar, N., Rosenstock, J., Pratley, R., et al. (2022). Efpeglenatide and clinical outcomes with and without concomitant sodium-glucose cotransporter-2 inhibition use in type 2 diabetes: exploratory analysis of the AMPLITUDE-O trial. _Circulation_ 145 (8), 565-574\. doi:10.1161/CIRCULATIONAHA.121.057934

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34775781/) | [CrossRef Full Text](https://doi.org/10.1161/CIRCULATIONAHA.121.057934) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Efpeglenatide+and+clinical+outcomes+with+and+without+concomitant+sodium-glucose+cotransporter-2+inhibition+use+in+type+2+diabetes:+exploratory+analysis+of+the+AMPLITUDE-O+trial&btnG=)

Lambadiari, V., Pavlidis, G., Kousathana, F., Varoudi, M., Vlastos, D., Maratou, E., et al. (2018). Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes. _Cardiovasc. Diabetol._ 17 (1), 8. doi:10.1186/s12933-017-0646-z

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29310645/) | [CrossRef Full Text](https://doi.org/10.1186/s12933-017-0646-z) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Effects+of+6-month+treatment+with+the+glucagon+like+peptide-1+analogue+liraglutide+on+arterial+stiffness,+left+ventricular+myocardial+deformation+and+oxidative+stress+in+subjects+with+newly+diagnosed+type+2+diabetes&btnG=)

Lenharo, M. (2023). Anti-obesity drug also protects against heart disease - what happens next? _Nature_ 620 (7974), 480. doi:10.1038/d41586-023-02528-2

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37568000/) | [CrossRef Full Text](https://doi.org/10.1038/d41586-023-02528-2) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Anti-obesity+drug+also+protects+against+heart+disease+-+what+happens+next?&btnG=)

Li, Z., Guo, J., and Bi, L. (2020a). Role of the NLRP3 inflammasome in autoimmune diseases. _Biomed. Pharmacother. = Biomedecine Pharmacother._ 130, 110542. doi:10.1016/j.biopha.2020.110542

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32738636/) | [CrossRef Full Text](https://doi.org/10.1016/j.biopha.2020.110542) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Role+of+the+NLRP3+inflammasome+in+autoimmune+diseases&btnG=)

Li, Z., Li, S., Wang, N., Xue, P., and Li, Y. (2020b). Liraglutide, a glucagon-like peptide-1 receptor agonist, suppresses osteoclastogenesis through the inhibition of NF-κB and MAPK pathways via GLP-1R. _Biomed. Pharmacother. = Biomedecine Pharmacother._ 130, 110523. doi:10.1016/j.biopha.2020.110523

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32702632/) | [CrossRef Full Text](https://doi.org/10.1016/j.biopha.2020.110523) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide,+a+glucagon-like+peptide-1+receptor+agonist,+suppresses+osteoclastogenesis+through+the+inhibition+of+NF-κB+and+MAPK+pathways+via+GLP-1R&btnG=)

Liaqat, A., Asad, M., Shoukat, F., and Khan, A.-U. (2020). A spotlight on the underlying activation mechanisms of the NLRP3 inflammasome and its role in atherosclerosis: a review. _Inflammation_ 43 (6), 2011-2020\. doi:10.1007/s10753-020-01290-1

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32656610/) | [CrossRef Full Text](https://doi.org/10.1007/s10753-020-01290-1) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=A+spotlight+on+the+underlying+activation+mechanisms+of+the+NLRP3+inflammasome+and+its+role+in+atherosclerosis:+a+review&btnG=)

Libby, P. (2021). Inflammation during the life cycle of the atherosclerotic plaque. _Cardiovasc. Res._ 117 (13), 2525-2536\. doi:10.1093/cvr/cvab303

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34550337/) | [CrossRef Full Text](https://doi.org/10.1093/cvr/cvab303) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Inflammation+during+the+life+cycle+of+the+atherosclerotic+plaque&btnG=)

Libby, P., Buring, J. E., Badimon, L., Hansson, G. K., Deanfield, J., Bittencourt, M. S., et al. (2019). Atherosclerosis. _Nat. Rev. Dis. Prim._ 5 (1), 56. doi:10.1038/s41572-019-0106-z

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31420554/) | [CrossRef Full Text](https://doi.org/10.1038/s41572-019-0106-z) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Atherosclerosis&btnG=)

Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., et al. (2023). Semaglutide and cardiovascular outcomes in obesity without diabetes. _N. Engl. J. Med._ 389 (24), 2221-2232\. doi:10.1056/NEJMoa2307563

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37952131/) | [CrossRef Full Text](https://doi.org/10.1056/NEJMoa2307563) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Semaglutide+and+cardiovascular+outcomes+in+obesity+without+diabetes&btnG=)

Lingvay, I., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., et al. (2023). Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics. _Obes. (Silver Spring, Md.)_ 31 (1), 111-122\. doi:10.1002/oby.23621

[CrossRef Full Text](https://doi.org/10.1002/oby.23621) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Semaglutide+for+cardiovascular+event+reduction+in+people+with+overweight+or+obesity:+SELECT+study+baseline+characteristics&btnG=)

Linton, M. F., Moslehi, J. J., and Babaev, V. R. (2019). Akt signaling in macrophage polarization, survival, and atherosclerosis. _Int. J. Mol. Sci._ 20 (11), 2703. doi:10.3390/ijms20112703

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31159424/) | [CrossRef Full Text](https://doi.org/10.3390/ijms20112703) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Akt+signaling+in+macrophage+polarization,+survival,+and+atherosclerosis&btnG=)

Liu, T., Zhao, D., and Qi, Y. (2022). Global trends in the epidemiology and management of dyslipidemia. _J. Clin. Med._ 11 (21), 6377. doi:10.3390/jcm11216377

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36362605/) | [CrossRef Full Text](https://doi.org/10.3390/jcm11216377) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Global+trends+in+the+epidemiology+and+management+of+dyslipidemia&btnG=)

Luna-Marco, C., de Marañon, A. M., Hermo-Argibay, A., Rodriguez-Hernandez, Y., Hermenejildo, J., Fernandez-Reyes, M., et al. (2023). Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes. _Redox Biol._ 66, 102849. doi:10.1016/j.redox.2023.102849

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37591012/) | [CrossRef Full Text](https://doi.org/10.1016/j.redox.2023.102849) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Effects+of+GLP-1+receptor+agonists+on+mitochondrial+function,+inflammatory+markers+and+leukocyte-endothelium+interactions+in+type+2+diabetes&btnG=)

Luo, X., Hu, Y., He, S., Ye, Q., Lv, Z., Liu, J., et al. (2019). Dulaglutide inhibits high glucose-induced endothelial dysfunction and NLRP3 inflammasome activation. _Archives Biochem. Biophysics_ 671, 203-209\. doi:10.1016/j.abb.2019.07.008

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31302140/) | [CrossRef Full Text](https://doi.org/10.1016/j.abb.2019.07.008) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Dulaglutide+inhibits+high+glucose-induced+endothelial+dysfunction+and+NLRP3+inflammasome+activation&btnG=)

Mann, J. F. E., Ørsted, D. D., Brown-Frandsen, K., Marso, S. P., Poulter, N. R., Rasmussen, S., et al. (2017). Liraglutide and renal outcomes in type 2 diabetes. _N. Engl. J. Med._ 377 (9), 839-848\. doi:10.1056/NEJMoa1616011

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/28854085/) | [CrossRef Full Text](https://doi.org/10.1056/NEJMoa1616011) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+and+renal+outcomes+in+type+2+diabetes&btnG=)

Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jodar, E., Leiter, L. A., et al. (2016a). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. _N. Engl. J. Med._ 375 (19), 1834-1844\. doi:10.1056/NEJMoa1607141

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/27633186/) | [CrossRef Full Text](https://doi.org/10.1056/NEJMoa1607141) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Semaglutide+and+cardiovascular+outcomes+in+patients+with+type+2+diabetes&btnG=)

Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., et al. (2016b). Liraglutide and cardiovascular outcomes in type 2 diabetes. _N. Engl. J. Med._ 375 (4), 311-322\. doi:10.1056/NEJMoa1603827

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/27295427/) | [CrossRef Full Text](https://doi.org/10.1056/NEJMoa1603827) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+and+cardiovascular+outcomes+in+type+2+diabetes&btnG=)

Martens, P., Mathieu, C., and Vanassche, T. (2023). The use of glucagon-like-peptide-1 receptor agonist in the cardiology practice. _Acta Cardiol._ 78 (5), 552-564\. doi:10.1080/00015385.2022.2076307

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35575294/) | [CrossRef Full Text](https://doi.org/10.1080/00015385.2022.2076307) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+use+of+glucagon-like-peptide-1+receptor+agonist+in+the+cardiology+practice&btnG=)

Martinez, G. J., Celermajer, D. S., and Patel, S. (2018). The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. _Atherosclerosis_ 269, 262-271\. doi:10.1016/j.atherosclerosis.2017.12.027

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29352570/) | [CrossRef Full Text](https://doi.org/10.1016/j.atherosclerosis.2017.12.027) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+NLRP3+inflammasome+and+the+emerging+role+of+colchicine+to+inhibit+atherosclerosis-associated+inflammation&btnG=)

Miano, J. M., Fisher, E. A., and Majesky, M. W. (2021). Fate and state of vascular smooth muscle cells in atherosclerosis. _Circulation_ 143 (21), 2110-2116\. doi:10.1161/CIRCULATIONAHA.120.049922

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34029141/) | [CrossRef Full Text](https://doi.org/10.1161/CIRCULATIONAHA.120.049922) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Fate+and+state+of+vascular+smooth+muscle+cells+in+atherosclerosis&btnG=)

Muskiet, M. H. A., Tonneijck, L., Huang, Y., Liu, M., Saremi, A., Heerspink, H. J. L., et al. (2018). Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial. _Lancet. Diabetes and Endocrinol._ 6 (11), 859-869\. doi:10.1016/S2213-8587(18)30268-7

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30292589/) | [CrossRef Full Text](https://doi.org/10.1016/S2213-8587\(18\)30268-7) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Lixisenatide+and+renal+outcomes+in+patients+with+type+2+diabetes+and+acute+coronary+syndrome:+an+exploratory+analysis+of+the+ELIXA+randomised,+placebo-controlled+trial&btnG=)

Nauck, M. A., and Muller, T. D. (2023). Incretin hormones and type 2 diabetes. _Diabetologia_ 66 (10), 1780-1795\. doi:10.1007/s00125-023-05956-x

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37430117/) | [CrossRef Full Text](https://doi.org/10.1007/s00125-023-05956-x) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Incretin+hormones+and+type+2+diabetes&btnG=)

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., et al. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. _BMJ Clin. Res. ed._ 372, n71. doi:10.1136/bmj.n71

[CrossRef Full Text](https://doi.org/10.1136/bmj.n71) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+PRISMA+2020+statement:+an+updated+guideline+for+reporting+systematic+reviews&btnG=)

Pan, X., Yang, L., Wang, S., Liu, Y., Yue, L., and Chen, S. (2023). Semaglutide alleviates inflammation-Induced endothelial progenitor cells injury by inhibiting MiR-155 expression in macrophage exosomes. _Int. Immunopharmacol._ 119, 110196. doi:10.1016/j.intimp.2023.110196

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37075674/) | [CrossRef Full Text](https://doi.org/10.1016/j.intimp.2023.110196) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Semaglutide+alleviates+inflammation-Induced+endothelial+progenitor+cells+injury+by+inhibiting+MiR-155+expression+in+macrophage+exosomes&btnG=)

Pfeffer, M. A., Claggett, B., Diaz, R., Dickstein, K., Gerstein, H. C., Køber, L. V., et al. (2015). Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. _N. Engl. J. Med._ 373 (23), 2247-2257\. doi:10.1056/NEJMoa1509225

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/26630143/) | [CrossRef Full Text](https://doi.org/10.1056/NEJMoa1509225) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Lixisenatide+in+patients+with+type+2+diabetes+and+acute+coronary+syndrome&btnG=)

Qin, J., and Song, L. (2022). Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of double-blind, randomized, placebo-controlled clinical trials. _BMC Endocr. Disord._ 22 (1), 125. doi:10.1186/s12902-022-01036-0

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35546664/) | [CrossRef Full Text](https://doi.org/10.1186/s12902-022-01036-0) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Glucagon-like+peptide-1+\(GLP-1\)+receptor+agonists+and+cardiovascular+events+in+patients+with+type+2+diabetes+mellitus:+a+meta-analysis+of+double-blind,+randomized,+placebo-controlled+clinical+trials&btnG=)

Rakipovski, G., Rolin, B., Nøhr, J., Klewe, I., Frederiksen, K. S., Augustin, R., et al. (2018). The GLP-1 analogs liraglutide and semaglutide reduce atherosclerosis in ApoE-/- and LDLr-/- mice by a mechanism that includes inflammatory pathways. _JACC. Basic Transl. Sci._ 3 (6), 844-857\. doi:10.1016/j.jacbts.2018.09.004

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30623143/) | [CrossRef Full Text](https://doi.org/10.1016/j.jacbts.2018.09.004) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+GLP-1+analogs+liraglutide+and+semaglutide+reduce+atherosclerosis+in+ApoE-/-+and+LDLr-/-+mice+by+a+mechanism+that+includes+inflammatory+pathways&btnG=)

Saraiva, J. F. K., and Franco, D. (2021). Oral GLP-1 analogue: perspectives and impact on atherosclerosis in type 2 diabetic patients. _Cardiovasc. Diabetol._ 20 (1), 235. doi:10.1186/s12933-021-01417-0

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34911560/) | [CrossRef Full Text](https://doi.org/10.1186/s12933-021-01417-0) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Oral+GLP-1+analogue:+perspectives+and+impact+on+atherosclerosis+in+type+2+diabetic+patients&btnG=)

Scheen, A. J. (2018). GLP-1 receptor agonists and cardiovascular protection: a class effect or not? _Diabetes and Metabolism_ 44 (3), 193-196\. doi:10.1016/j.diabet.2017.12.009

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/29551531/) | [CrossRef Full Text](https://doi.org/10.1016/j.diabet.2017.12.009) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=GLP-1+receptor+agonists+and+cardiovascular+protection:+a+class+effect+or+not?&btnG=)

Schubert, M., Hansen, S., Leefmann, J., and Guan, K. (2020). Repurposing antidiabetic drugs for cardiovascular disease. _Front. Physiology_ 11, 568632. doi:10.3389/fphys.2020.568632

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/33041865/) | [CrossRef Full Text](https://doi.org/10.3389/fphys.2020.568632) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Repurposing+antidiabetic+drugs+for+cardiovascular+disease&btnG=)

Scott, L. J. (2020). Dulaglutide: a review in type 2 diabetes. _Drugs_ 80 (2), 197-208\. doi:10.1007/s40265-020-01260-9

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32002850/) | [CrossRef Full Text](https://doi.org/10.1007/s40265-020-01260-9) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Dulaglutide:+a+review+in+type+2+diabetes&btnG=)

Senoner, T., and Dichtl, W. (2019). Oxidative stress in cardiovascular diseases: still a therapeutic target? _Nutrients_ 11 (9), 2090. doi:10.3390/nu11092090

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31487802/) | [CrossRef Full Text](https://doi.org/10.3390/nu11092090) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Oxidative+stress+in+cardiovascular+diseases:+still+a+therapeutic+target?&btnG=)

Shah, P. K. (2019). Inflammation, infection and atherosclerosis. _Trends Cardiovasc. Med._ 29 (8), 468-472\. doi:10.1016/j.tcm.2019.01.004

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30733074/) | [CrossRef Full Text](https://doi.org/10.1016/j.tcm.2019.01.004) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Inflammation,+infection+and+atherosclerosis&btnG=)

Shi, J., Yang, Y., Cheng, A., Xu, G., and He, F. (2020). Metabolism of vascular smooth muscle cells in vascular diseases. _Am. J. Physiology. Heart Circulatory Physiology_ 319 (3), H613-H631-H631. doi:10.1152/ajpheart.00220.2020

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32762559/) | [CrossRef Full Text](https://doi.org/10.1152/ajpheart.00220.2020) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Metabolism+of+vascular+smooth+muscle+cells+in+vascular+diseases&btnG=)

Sivalingam, S., Larsen, E. L., van Raalte, D. H., Muskiet, M. H. A., Smits, M. M., Tonneijck, L., et al. (2021). The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes. _Sci. Rep._ 11 (1), 10624. doi:10.1038/s41598-021-90191-w

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34012064/) | [CrossRef Full Text](https://doi.org/10.1038/s41598-021-90191-w) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+effect+of+liraglutide+and+sitagliptin+on+oxidative+stress+in+persons+with+type+2+diabetes&btnG=)

Song, S., Guo, R., Mehmood, A., Zhang, L., Yin, B., Yuan, C., et al. (2022). Liraglutide attenuate central nervous inflammation and demyelination through AMPK and pyroptosis-related NLRP3 pathway. _CNS Neurosci. Ther._ 28 (3), 422-434\. doi:10.1111/cns.13791

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34985189/) | [CrossRef Full Text](https://doi.org/10.1111/cns.13791) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+attenuate+central+nervous+inflammation+and+demyelination+through+AMPK+and+pyroptosis-related+NLRP3+pathway&btnG=)

Sposito, A. C., Berwanger, O., de Carvalho, L. S. F., and Saraiva, J. F. K. (2018). GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data. _Cardiovasc. Diabetol._ 17 (1), 157. doi:10.1186/s12933-018-0800-2

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30545359/) | [CrossRef Full Text](https://doi.org/10.1186/s12933-018-0800-2) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=GLP-1RAs+in+type+2+diabetes:+mechanisms+that+underlie+cardiovascular+effects+and+overview+of+cardiovascular+outcome+data&btnG=)

Tanase, D. M., Valasciuc, E., Gosav, E. M., Ouatu, A., Buliga-Finis, O. N., Floria, M., et al. (2023). Portrayal of NLRP3 inflammasome in atherosclerosis: current knowledge and therapeutic targets. _Int. J. Mol. Sci._ 24 (9), 8162. doi:10.3390/ijms24098162

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37175869/) | [CrossRef Full Text](https://doi.org/10.3390/ijms24098162) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Portrayal+of+NLRP3+inflammasome+in+atherosclerosis:+current+knowledge+and+therapeutic+targets&btnG=)

Tang, Z., Liu, L., Guo, Y., Deng, G., Chen, M., and Wei, J. (2018). Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway. _Mol. Med. Rep._ 18 (3), 3350-3358\. doi:10.3892/mmr.2018.9345

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30085331/) | [CrossRef Full Text](https://doi.org/10.3892/mmr.2018.9345) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Exendin-4+reverses+endothelial+dysfunction+in+mice+fed+a+high-cholesterol+diet+by+a+GTP+cyclohydrolase-1/tetrahydrobiopterin+pathway&btnG=)

Tashiro, Y., Sato, K., Watanabe, T., Nohtomi, K., Terasaki, M., Nagashima, M., et al. (2014). A glucagon-like peptide-1 analog liraglutide suppresses macrophage foam cell formation and atherosclerosis. _Peptides_ 54, 19-26\. doi:10.1016/j.peptides.2013.12.015

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/24418070/) | [CrossRef Full Text](https://doi.org/10.1016/j.peptides.2013.12.015) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=A+glucagon-like+peptide-1+analog+liraglutide+suppresses+macrophage+foam+cell+formation+and+atherosclerosis&btnG=)

Thomas, M. C., Coughlan, M. T., and Cooper, M. E. (2023). The postprandial actions of GLP-1 receptor agonists: the missing link for cardiovascular and kidney protection in type 2 diabetes. _Cell. Metab._ 35 (2), 253-273\. doi:10.1016/j.cmet.2023.01.004

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36754019/) | [CrossRef Full Text](https://doi.org/10.1016/j.cmet.2023.01.004) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+postprandial+actions+of+GLP-1+receptor+agonists:+the+missing+link+for+cardiovascular+and+kidney+protection+in+type+2+diabetes&btnG=)

Tilinca, M. C., Tiuca, R. A., Niculas, C., Varga, A., and Tilea, I. (2021). Future perspectives in diabesity treatment: semaglutide, a glucagon-like peptide 1 receptor agonist (Review). _Exp. Ther. Med._ 22 (4), 1167. doi:10.3892/etm.2021.10601

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34504612/) | [CrossRef Full Text](https://doi.org/10.3892/etm.2021.10601) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Future+perspectives+in+diabesity+treatment:+semaglutide,+a+glucagon-like+peptide+1+receptor+agonist+\(Review\)&btnG=)

Tommerdahl, K. L., Kendrick, J., and Bjornstad, P. (2022). The role of glucagon-like peptide 1 (GLP-1) receptor agonists in the prevention and treatment of diabetic kidney disease: insights from the AMPLITUDE-O trial. _Clin. J. Am. Soc. Nephrol. CJASN_ 17 (6), 905-907\. doi:10.2215/CJN.00020122

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35396319/) | [CrossRef Full Text](https://doi.org/10.2215/CJN.00020122) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+role+of+glucagon-like+peptide+1+\(GLP-1\)+receptor+agonists+in+the+prevention+and+treatment+of+diabetic+kidney+disease:+insights+from+the+AMPLITUDE-O+trial&btnG=)

Trujillo, J. M., Nuffer, W., and Smith, B. A. (2021). GLP-1 receptor agonists: an updated review of head-to-head clinical studies. _Ther. Adv. Endocrinol. Metabolism_ 12, 2042018821997320. doi:10.1177/2042018821997320

[CrossRef Full Text](https://doi.org/10.1177/2042018821997320) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=GLP-1+receptor+agonists:+an+updated+review+of+head-to-head+clinical+studies&btnG=)

Ussher, J. R., and Drucker, D. J. (2023). Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. _Nat. Rev. Cardiol._ 20 (7), 463-474\. doi:10.1038/s41569-023-00849-3

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36977782/) | [CrossRef Full Text](https://doi.org/10.1038/s41569-023-00849-3) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Glucagon-like+peptide+1+receptor+agonists:+cardiovascular+benefits+and+mechanisms+of+action&btnG=)

Valanti, E.-K., Dalakoura-Karagkouni, K., Siasos, G., Kardassis, D., Eliopoulos, A. G., and Sanoudou, D. (2021). Advances in biological therapies for dyslipidemias and atherosclerosis. _Metabolism Clin. Exp._ 116, 154461. doi:10.1016/j.metabol.2020.154461

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/33290761/) | [CrossRef Full Text](https://doi.org/10.1016/j.metabol.2020.154461) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Advances+in+biological+therapies+for+dyslipidemias+and+atherosclerosis&btnG=)

Vandemark, C., Nguyen, J., and Zhao, Z.-Q. (2023). Cardiovascular protection with a long-acting GLP-1 receptor agonist liraglutide: an experimental update. _Mol. Basel, Switz._ 28 (3), 1369. doi:10.3390/molecules28031369

[CrossRef Full Text](https://doi.org/10.3390/molecules28031369) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Cardiovascular+protection+with+a+long-acting+GLP-1+receptor+agonist+liraglutide:+an+experimental+update&btnG=)

Verma, S., McGuire, D. K., Bain, S. C., Bhatt, D. L., Leiter, L. A., Mazer, C. D., et al. (2020). Effects of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: results of the LEADER and SUSTAIN 6 trials. _Diabetes, Obes. Metabolism_ 22 (12), 2487-2492\. doi:10.1111/dom.14160

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32744418/) | [CrossRef Full Text](https://doi.org/10.1111/dom.14160) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Effects+of+glucagon-like+peptide-1+receptor+agonists+liraglutide+and+semaglutide+on+cardiovascular+and+renal+outcomes+across+body+mass+index+categories+in+type+2+diabetes:+results+of+the+LEADER+and+SUSTAIN+6+trials&btnG=)

Wang, C., Niimi, M., Watanabe, T., Wang, Y., Liang, J., and Fan, J. (2018). Treatment of atherosclerosis by traditional Chinese medicine: questions and quandaries. _Atherosclerosis_ 277, 136-144\. doi:10.1016/j.atherosclerosis.2018.08.039

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30212682/) | [CrossRef Full Text](https://doi.org/10.1016/j.atherosclerosis.2018.08.039) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Treatment+of+atherosclerosis+by+traditional+Chinese+medicine:+questions+and+quandaries&btnG=)

Wang, L., and Hauenstein, A. V. (2020). The NLRP3 inflammasome: mechanism of action, role in disease and therapies. _Mol. Aspects Med._ 76, 100889. doi:10.1016/j.mam.2020.100889

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32859386/) | [CrossRef Full Text](https://doi.org/10.1016/j.mam.2020.100889) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+NLRP3+inflammasome:+mechanism+of+action,+role+in+disease+and+therapies&btnG=)

Wang, Q., Wang, T., Liang, S., and Zhou, L. (2023a). Ox-LDL-induced vascular smooth muscle cell dysfunction partly depends on the circ_0044073/miR-377-3p/AURKA Axis in atherosclerosis. _Int. Heart J._ 64 (2), 252-262\. doi:10.1536/ihj.22-148

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37005319/) | [CrossRef Full Text](https://doi.org/10.1536/ihj.22-148) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Ox-LDL-induced+vascular+smooth+muscle+cell+dysfunction+partly+depends+on+the+circ_0044073/miR-377-3p/AURKA+Axis+in+atherosclerosis&btnG=)

Wang, W., and Kang, P. M. (2020). Oxidative stress and antioxidant treatments in cardiovascular diseases. _Antioxidants Basel, Switz._ 9 (12), 1292. doi:10.3390/antiox9121292

[CrossRef Full Text](https://doi.org/10.3390/antiox9121292) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Oxidative+stress+and+antioxidant+treatments+in+cardiovascular+diseases&btnG=)

Wang, W., Mei, A., Qian, H., Li, D., Xu, H., Chen, J., et al. (2023b). The role of glucagon-like peptide-1 receptor agonists in chronic obstructive pulmonary disease. _Int. J. Chronic Obstr. Pulm. Dis._ 18, 129-137\. doi:10.2147/COPD.S393323

[CrossRef Full Text](https://doi.org/10.2147/COPD.S393323) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+role+of+glucagon-like+peptide-1+receptor+agonists+in+chronic+obstructive+pulmonary+disease&btnG=)

Webb, J., Mount, J., von Arx, L.-B., Rachman, J., Spanopoulos, D., Wood, R., et al. (2022). Cardiovascular risk profiles: a cross-sectional study evaluating the generalizability of the glucagon-like peptide-1 receptor agonist cardiovascular outcome trials REWIND, LEADER and SUSTAIN-6 to the real-world type 2 diabetes population in the United Kingdom. _Diabetes, Obes. Metabolism_ 24 (2), 289-295\. doi:10.1111/dom.14580

[CrossRef Full Text](https://doi.org/10.1111/dom.14580) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Cardiovascular+risk+profiles:+a+cross-sectional+study+evaluating+the+generalizability+of+the+glucagon-like+peptide-1+receptor+agonist+cardiovascular+outcome+trials+REWIND,+LEADER+and+SUSTAIN-6+to+the+real-world+type+2+diabetes+population+in+the+United+Kingdom&btnG=)

Wei, R., Ma, S., Wang, C., Ke, J., Yang, J., Li, W., et al. (2016). Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1 receptor-dependent manner. _Am. J. Physiology. Endocrinol. Metabolism_ 310 (11), E947-E957. doi:10.1152/ajpendo.00400.2015

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/27072494/) | [CrossRef Full Text](https://doi.org/10.1152/ajpendo.00400.2015) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Exenatide+exerts+direct+protective+effects+on+endothelial+cells+through+the+AMPK/Akt/eNOS+pathway+in+a+GLP-1+receptor-dependent+manner&btnG=)

Wu, H., Xiao, C., Zhao, Y., Yin, H., and Yu, M. (2021). Liraglutide improves endothelial function via the mTOR signaling pathway. _J. Diabetes Res._ 2021, 2936667. doi:10.1155/2021/2936667

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/34447854/) | [CrossRef Full Text](https://doi.org/10.1155/2021/2936667) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+improves+endothelial+function+via+the+mTOR+signaling+pathway&btnG=)

Xiao, M., Lu, D., Tian, J., Yu, Y., Zhang, Q., Zhang, L., et al. (2020). The protective effects of GLP-1 receptor agonist lixisenatide on oxygen-glucose deprivation/reperfusion (OGD/R)-induced deregulation of endothelial tube formation. _RSC Adv._ 10 (17), 10245-10253\. doi:10.1039/c9ra09959j

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/35498599/) | [CrossRef Full Text](https://doi.org/10.1039/c9ra09959j) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+protective+effects+of+GLP-1+receptor+agonist+lixisenatide+on+oxygen-glucose+deprivation/reperfusion+\(OGD/R\)-induced+deregulation+of+endothelial+tube+formation&btnG=)

Xu, X.-D., Chen, J.-X., Zhu, L., Xu, S.-T., Jiang, J., and Ren, K. (2022). The emerging role of pyroptosis-related inflammasome pathway in atherosclerosis. _Mol. Med._ 28 (1), 160. doi:10.1186/s10020-022-00594-2

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36544112/) | [CrossRef Full Text](https://doi.org/10.1186/s10020-022-00594-2) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+emerging+role+of+pyroptosis-related+inflammasome+pathway+in+atherosclerosis&btnG=)

Yan, Q., Liu, S., Sun, Y., Chen, C., Yang, S., Lin, M., et al. (2023). Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease. _J. Transl. Med._ 21 (1), 519. doi:10.1186/s12967-023-04361-7

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37533007/) | [CrossRef Full Text](https://doi.org/10.1186/s12967-023-04361-7) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Targeting+oxidative+stress+as+a+preventive+and+therapeutic+approach+for+cardiovascular+disease&btnG=)

Yang, L., Chen, L., Li, D., Xu, H., Chen, J., Min, X., et al. (2021). Effect of GLP-1/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis. _Mediat. Inflamm._ 2021, 5568159. doi:10.1155/2021/5568159

[CrossRef Full Text](https://doi.org/10.1155/2021/5568159) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Effect+of+GLP-1/GLP-1R+on+the+polarization+of+macrophages+in+the+occurrence+and+development+of+atherosclerosis&btnG=)

Ye, T., Tao, W.-Y., Chen, X.-Y., Jiang, C., Di, B., and Xu, L.-L. (2023). Mechanisms of NLRP3 inflammasome activation and the development of peptide inhibitors. _Cytokine and Growth Factor Rev._ 74, 1-13\. doi:10.1016/j.cytogfr.2023.09.007

[CrossRef Full Text](https://doi.org/10.1016/j.cytogfr.2023.09.007) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Mechanisms+of+NLRP3+inflammasome+activation+and+the+development+of+peptide+inhibitors&btnG=)

Yu, W., Jiang, W., Wu, W., Wang, G., Zhao, D., Yan, C., et al. (2023). Combining idebenone and rosuvastatin prevents atherosclerosis by suppressing oxidative stress and NLRP3 inflammasome activation. _Eur. J. Pharmacol._ 955, 175911. doi:10.1016/j.ejphar.2023.175911

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/37451421/) | [CrossRef Full Text](https://doi.org/10.1016/j.ejphar.2023.175911) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Combining+idebenone+and+rosuvastatin+prevents+atherosclerosis+by+suppressing+oxidative+stress+and+NLRP3+inflammasome+activation&btnG=)

Yue, W., Li, Y., Ou, D., and Yang, Q. (2019). The GLP-1 receptor agonist liraglutide protects against oxidized LDL-induced endothelial inflammation and dysfunction via KLF2. _IUBMB Life_ 71 (9), 1347-1354\. doi:10.1002/iub.2046

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/30969479/) | [CrossRef Full Text](https://doi.org/10.1002/iub.2046) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=The+GLP-1+receptor+agonist+liraglutide+protects+against+oxidized+LDL-induced+endothelial+inflammation+and+dysfunction+via+KLF2&btnG=)

Zhang, L., Tian, J., Diao, S., Zhang, G., Xiao, M., and Chang, D. (2020). GLP-1 receptor agonist liraglutide protects cardiomyocytes from IL-1β-induced metabolic disturbance and mitochondrial dysfunction. _Chemico-biological Interact._ 332, 109252. doi:10.1016/j.cbi.2020.109252

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/32898504/) | [CrossRef Full Text](https://doi.org/10.1016/j.cbi.2020.109252) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=GLP-1+receptor+agonist+liraglutide+protects+cardiomyocytes+from+IL-1β-induced+metabolic+disturbance+and+mitochondrial+dysfunction&btnG=)

Zhang, W.-J., Li, K.-Y., Lan, Y., Zeng, H.-Y., Chen, S.-Q., and Wang, H. (2023). NLRP3 Inflammasome: a key contributor to the inflammation formation. _Food Chem. Toxicol. Int. J. Publ. Br. Industrial Biol. Res. Assoc._ 174, 113683. doi:10.1016/j.fct.2023.113683

[CrossRef Full Text](https://doi.org/10.1016/j.fct.2023.113683) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=NLRP3+Inflammasome:+a+key+contributor+to+the+inflammation+formation&btnG=)

Zheng, R.-H., Bai, X.-J., Zhang, W.-W., Wang, J., Bai, F., Yan, C.-P., et al. (2019). Liraglutide attenuates cardiac remodeling and improves heart function after abdominal aortic constriction through blocking angiotensin II type 1 receptor in rats. _Drug Des. Dev. Ther._ 13, 2745-2757\. doi:10.2147/DDDT.S213910

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31496651/) | [CrossRef Full Text](https://doi.org/10.2147/DDDT.S213910) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+attenuates+cardiac+remodeling+and+improves+heart+function+after+abdominal+aortic+constriction+through+blocking+angiotensin+II+type+1+receptor+in+rats&btnG=)

Zhou, G., Wu, H., Yang, J., Ye, M., Liu, D., Li, Y., et al. (2023). Liraglutide attenuates myocardial ischemia/reperfusion injury through the inhibition of necroptosis by activating GLP-1R/PI3K/akt pathway. _Cardiovasc. Toxicol._ 23 (3-4), 161-175\. doi:10.1007/s12012-023-09789-3

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/36934206/) | [CrossRef Full Text](https://doi.org/10.1007/s12012-023-09789-3) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Liraglutide+attenuates+myocardial+ischemia/reperfusion+injury+through+the+inhibition+of+necroptosis+by+activating+GLP-1R/PI3K/akt+pathway&btnG=)

Zhu, J., Liu, B., Wang, Z., Wang, D., Ni, H., Zhang, L., et al. (2019). Exosomes from nicotine-stimulated macrophages accelerate atherosclerosis through miR-21-3p/PTEN-mediated VSMC migration and proliferation. _Theranostics_ 9 (23), 6901-6919\. doi:10.7150/thno.37357

[PubMed Abstract](https://pubmed.ncbi.nlm.nih.gov/31660076/) | [CrossRef Full Text](https://doi.org/10.7150/thno.37357) | [Google Scholar](https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Exosomes+from+nicotine-stimulated+macrophages+accelerate+atherosclerosis+through+miR-21-3p/PTEN-mediated+VSMC+migration+and+proliferation&btnG=)

Keywords: glucagon-like peptide-1 receptor agonists, atherosclerosis, cardiovascular outcome trials, inflammation, mitochondrial dysfunction

Citation: Wang T, Ding J, Cheng X, Yang Q and Hu P (2024) Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease. _Front. Pharmacol._ 15:1396656. doi: 10.3389/fphar.2024.1396656

Received: 06 March 2024; Accepted: 11 April 2024;  
Published: 24 April 2024.

Edited by:

[Mahmoud El-Mas](https://loop.frontiersin.org/people/475616/overview), Alexandria University, Egypt

Reviewed by:

[Raffaele Carraro](https://loop.frontiersin.org/people/1599117/overview), La Princesa University Hospital, Spain  
[Zhijun Meng](https://loop.frontiersin.org/people/1947728/overview), Shanxi Provincial People's Hospital, China

Copyright (C) 2024 Wang, Ding, Cheng, Yang and Hu. This is an open-access article distributed under the terms of the [Creative Commons Attribution License (CC BY).](http://creativecommons.org/licenses/by/4.0/) The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Pengfei Hu, MjAwNjQwMTJAemNtdS5lZHUuY24=

Disclaimer:  All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. 

Download article

  * [ Download PDF ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/pdf)
  * [ ReadCube ](http://www.readcube.com/articles/10.3389/fphar.2024.1396656)
  * [ EPUB ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/epub)
  * [ XML (NLM) ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/xml/nlm)



Share on

  * [](https://www.twitter.com/share?url=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1396656/full "Share on X")
  * [](https://www.linkedin.com/share?url=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1396656/full "Share on Linkedin")
  * [](https://www.facebook.com/sharer/sharer.php?u=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1396656/full "Share on Facebook")



Export citation 

  * [ EndNote ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/endNote)
  * [ Reference Manager ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/reference)
  * [ Simple Text file ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/text)
  * [ BibTex ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/bibTex)



2,3K 

Total views

1K 

Downloads

1 

Citations

Citation numbers are available from Dimensions 

[View article impact](http://loop-impact.frontiersin.org/impact/article/1396656#totalviews/views)

[View altmetric score](https://www.altmetric.com/details/doi/10.3389/fphar.2024.1396656)

Share on

  * [](https://www.twitter.com/share?url=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1396656/full "Share on X")
  * [](https://www.linkedin.com/share?url=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1396656/full "Share on Linkedin")
  * [](https://www.facebook.com/sharer/sharer.php?u=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1396656/full "Share on Facebook")



Edited by

[![Mahmoud El-Mas](https://loop.frontiersin.org/images/profile/475616/32) Mahmoud El-Mas  Alexandria University, Egypt ](https://loop.frontiersin.org/people/475616/overview)

Reviewed by

[![Raffaele Carraro](https://loop.frontiersin.org/images/profile/1599117/32) Raffaele Carraro  Obesity Unit, La Princesa University Hospital, Spain ](https://loop.frontiersin.org/people/1599117/overview)[![Zhijun Meng](https://loop.frontiersin.org/images/profile/1947728/32) Zhijun Meng  Shanxi Provincial People's Hospital, China ](https://loop.frontiersin.org/people/1947728/overview)

Table of contents

  * Abstract
  * 1 Introduction
  * 2 Methods
  * 3 GLP-1 and its receptors
  * 4 CVOTs of GLP-1RAs
  * 5 Molecular mechanism of anti-AS by GLP-1RAs
  * 6 Conclusion
  * Author contributions
  * Funding
  * Acknowledgments
  * Conflict of interest
  * Publisher's note
  * References



Export citation

  * [ EndNote ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/endNote)
  * [ Reference Manager ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/reference)
  * [ Simple Text file ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/text)
  * [ BibTex ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/bibTex)



![Crossmark icon](/article-pages/_nuxt/img/crossmark.5c8ec60.svg)

Check for updates

Research integrity at Frontiers 

![Man ultramarathon runner in the mountains he trains at sunset](https://d2csxpduxe849s.cloudfront.net/media/E32629C6-9347-4F84-81FEAEF7BFA342B3/0B4B1380-42EB-4FD5-9D7E2DBC603E79F8/webimage-C4875379-1478-416F-B03DF68FE3D8DBB5.png)

## 94% of researchers rate our articles as excellent or good

Learn more about the work of our research integrity team to safeguard the quality of each article we publish.

  
[Find out more ](https://www.frontiersin.org/about/research-integrity)

Download article

Download 

  * [ Download PDF ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/pdf)
  * [ ReadCube ](http://www.readcube.com/articles/10.3389/fphar.2024.1396656)
  * [ EPUB ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/epub)
  * [ XML (NLM) ](/journals/pharmacology/articles/10.3389/fphar.2024.1396656/xml/nlm)



Research integrity at Frontiers 

![Man ultramarathon runner in the mountains he trains at sunset](https://d2csxpduxe849s.cloudfront.net/media/E32629C6-9347-4F84-81FEAEF7BFA342B3/0B4B1380-42EB-4FD5-9D7E2DBC603E79F8/webimage-C4875379-1478-416F-B03DF68FE3D8DBB5.png)

## 94% of researchers rate our articles as excellent or good

Learn more about the work of our research integrity team to safeguard the quality of each article we publish.

  
[Find out more ](https://www.frontiersin.org/about/research-integrity)

  * Guidelines

    * [Author guidelines](https://www.frontiersin.org/guidelines/author-guidelines)
    * [Editor guidelines](https://www.frontiersin.org/guidelines/editor-guidelines)
    * [Policies and publication ethics](https://www.frontiersin.org/guidelines/policies-and-publication-ethics)
    * [Fee policy](https://www.frontiersin.org/about/fee-policy)

  * Explore

    * [Articles](https://www.frontiersin.org/articles)
    * [Research Topics ](https://www.frontiersin.org/research-topics)
    * [Journals](https://www.frontiersin.org/journals)
    * [How we publish](https://www.frontiersin.org/about/how-we-publish)

  * Outreach

    * [Frontiers Forum ](https://forum.frontiersin.org/)
    * [Frontiers Policy Labs ](https://policylabs.frontiersin.org/)
    * [Frontiers for Young Minds](https://kids.frontiersin.org/)
    * [Frontiers Planet Prize](https://www.frontiersplanetprize.org/)

  * Connect

    * [Help center](https://helpcenter.frontiersin.org)
    * [Emails and alerts ](https://loop.frontiersin.org/settings/email-preferences?a=publishers)
    * [Contact us ](https://www.frontiersin.org/about/contact)
    * [Submit](https://www.frontiersin.org/submission/submit)
    * [Career opportunities](https://careers.frontiersin.org/)




Follow us

[](https://www.facebook.com/Frontiersin)[](https://twitter.com/frontiersin)[](https://www.linkedin.com/company/frontiers)[](https://www.instagram.com/frontiersin_)

© 2025 Frontiers Media S.A. All rights reserved

[Privacy policy](https://www.frontiersin.org/legal/privacy-policy) | [Terms and conditions](https://www.frontiersin.org/legal/terms-and-conditions)


title: Addressing muscle loss associated with GLP-1 medication use | TechTarget
scrape_date: 2025-02-28T09:09:39.667368
content_type: markdown
hash: 4cd6e1790d127a451a7fcd065231ad1012325e130ed13e12f830fe8d627b3d48
url:
https://www.techtarget.com/pharmalifesciences/answer/Addressing-muscle-loss-associated-with-GLP-1-medication-use

content:
__ xtelligent Pharma Life Sciences __ Search the TechTarget Network __

[Login](https://www.techtarget.com/login) [Register](https://www.techtarget.com/register)

[Explore the Network]()

  * [TechTarget Network](https://www.techtarget.com/network/)
  * [Healthtech Analytics](https://www.techtarget.com/healthtechanalytics/)
  * [Healthcare Payers](https://www.techtarget.com/healthcarepayers/)
  * [Health IT](https://www.techtarget.com/searchhealthit/)
  * [HealthtechSecurity](https://www.techtarget.com/healthtechsecurity/)



  * [ xtelligent Pharma Life Sciences ](https://www.techtarget.com/pharmalifesciences/)

  *     * [Biotechnology ](https://www.techtarget.com/pharmalifesciences/resources/Biotechnology-in-medicine)
    * [Clinical trials & RWE](https://www.techtarget.com/pharmalifesciences/resources/Clinical-trials-and-evidence)
    * [Genetics & genomics](https://www.techtarget.com/pharmalifesciences/resources/Genetics-and-genomics-in-medicine)
    * [Medical devices & imaging](https://www.techtarget.com/pharmalifesciences/resources/Medical-devices-and-imaging-technology)
    * [Mergers & acquisitions ](https://www.techtarget.com/pharmalifesciences/resources/Mergers-and-acquisitions-in-pharma-and-biotech)
    * More Topics __

      * [Pharmaceuticals](https://www.techtarget.com/pharmalifesciences/resources/Pharmaceuticals)
      * [Policy & regulation ](https://www.techtarget.com/pharmalifesciences/resources/Medical-policy-and-regulation)
      * [Research & development](https://www.techtarget.com/pharmalifesciences/resources/Medical-research-and-development)

Other Content
    * [News](https://www.techtarget.com/news/)
    * [Features](https://www.techtarget.com/pharmalifesciences/features)
    * [Webinars](https://www.techtarget.com/pharmalifesciences/webinars)
    * [White Papers](https://www.bitpipe.com/xt/keyword/Pharmaceutical)
    * [Sponsored Sites](https://www.techtarget.com/pharmalifesciences/sponsored_communities)



  * Follow:
  * [__](https://x.com/pharmanewsintel)
  * [__](https://www.linkedin.com/showcase/pharmanewsintelligence)



  * [Home](https://www.techtarget.com/pharmalifesciences/)
  * [Clinical trials and evidence](https://www.techtarget.com/pharmalifesciences/resources/Clinical-trials-and-evidence)



![](https://www.techtarget.com/rms/onlineimages/folder-files09_searchsitetablet_520X173.jpg)

Getty Images/iStockphoto

[Answer](https://www.techtarget.com/pharmalifesciences/answers)

# Addressing muscle loss associated with GLP-1 medication use

## Scholar Rock is running a proof-of-concept study to mitigate muscle loss and enhance muscle mass in patients using GLP-1 drugs for weight management.

  * Share this item with your network:
  * __
  * __
  * __
  * __
  * __



  * __
  * __
  * __
    * __
    * __
    * __
    * __



![Veronica Salib](https://cdn.ttgtmedia.com/rms/onlineImages/salib_veronica.jpg)

By

  * [Veronica Salib,](https://www.techtarget.com/contributor/Veronica-Salib) Associate Editor



Published: 02 Apr 2024

[Glucagon-like peptide-1 (GLP-1) receptor agonists](https://www.techtarget.com/pharmalifesciences/answer/Exploring-and-Managing-GLP-1-Receptor-Agonists-in-Weight-Loss) — also known as GLP-1 drugs — have gained a significant amount of attention in recent years because of their utility in managing type 2 diabetes (T2D) and, even more so, in weight management for overweight or obese adults. Despite the scientifically proven benefits of these drugs, there are many challenges posed by their use.

Among these challenges is muscle loss. For example, a [study on semaglutide](https://www.nejm.org/doi/full/10.1056/NEJMoa2032183) in the _New England Journal of Medicine_ showed a decline in lean mass in patients taking a weekly subcutaneous injection of the drug.

“Anywhere between 20% and 40% of the total weight [loss can] come from losing muscle mass,” Jay Backstrom, MD, MPH, President and CEO of Scholar Rock, explained in an interview with _PharmaNewsIntelligence_. “Inherently, that is problematic, [considering] the role that muscle plays.”

Retaining muscle mass is beneficial for multiple reasons. It improves bone health and metabolic function, among other factors. According to the National Institute of Arthritis and Musculoskeletal and Skin Disease, a part of the NIH, [muscle is critical for multiple bodily functions](https://www.niams.nih.gov/health-topics/kids/healthy-muscles#:~:text=your%20body%20strong.-,Healthy%20muscles%20let%20you%20move%20freely%20and%20keep%20your%20body,carpet%2C%20or%20mowing%20the%20lawn.). Beyond strengthening the body and providing more effortless movement, skeletal muscle helps with posture and balance. Smooth muscle in the body plays an essential role in the digestive system, and cardiac muscle helps ensure adequate and proper blood flow.

Although losing muscle mass is a natural byproduct of aging, for certain patients, the risk of losing muscle mass is enough of a concern that it contraindicates the [use of weight-loss drugs](https://www.techtarget.com/pharmalifesciences/feature/Guiding-Obesity-Management-by-Understanding-Weight-Loss-Drugs). For example, patients 65 and older who are already at risk of muscle loss may hesitate to begin GLP-1 medications because of the risk of muscle loss.

## __Myostatin

“Scholar rock was really founded on our ability to understand how to selectively and safely target a family of growth factors, one of which is myostatin, which is the key regulator of muscle,” noted Backstrom.

He said that myostatin is considered the master regulator of muscle mass, inhibiting its growth. In pre-clinical and clinical studies, blocking myostatin helps increase muscle mass and function. In other contexts, aside from weight loss, such as spinal muscular atrophy, researchers have proven the utility of blocking myostatin to increase muscle mass. Multiple studies, including a [2021 mouse study published in _Nutrients_](https://www.mdpi.com/2072-6643/13/5/1508), have demonstrated that blocking myostatin is beneficial for building muscle mass.

Understanding this connection, Scholar Rock is exploring how myostatin inhibitors that enhance muscle can work alongside weight loss drugs, such as GLP-1 drugs, that can cause muscle loss.

## __Enhancing the Impact of GLP-1 Drugs

“When we look at the models that everyone uses to understand the effect on weight, we're seeing that we have the potential to actually enhance the effects of the GLP-1 receptor agonists nicely, not just preserving and maintaining that muscle mass, but because muscle plays such a role in metabolism,” Backstrom continued. “We believe that we can enhance the profile of the GLP-1 receptor agonist by bringing those good effective outcomes from targeting the muscle, enhancing muscle, and its effect on metabolism.”

Muscle impacts how glucose is metabolized and increases insulin sensitivity, prompting an additive effect when combined with GLP-1 medications. Backstrom explained that muscle matters in healthy, sustainable weight loss management.

“If we restore and maintain that muscle, it'll do its job. It'll uptake glucose; it'll protect against insulin resistance. And because muscle is the major energy consumer, basal metabolic rate will be enhanced,” he said. “It's all about energy metabolism or energy balance that also might be able to reduce the amount of GLP-1 receptor agonist that [a patient] needs.”

GLP-1 drugs are a relatively new class of medications, which means there is limited understanding of their long-term effects; however, the short-term effects include gastrointestinal upset, which is dose-dependent. Higher doses correlate with an increased probability of experiencing side effects, but by optimizing weight loss with a myostatin inhibitor, patients may be able to take lower GLP-1 doses.

## __Proof-of-Concept Study

Scholar Rock is launching a proof-of-concept study to test this theory. Backstrom explained that the proof-of-concept study on the drug is rooted in the company’s previous work on spinal muscular atrophy (SMA). However, this study is focused on whether they can enhance or preserve muscle for patients on a GLP-1 drug, which has been known to reduce muscle mass. Data from the clinical trial are expected in 2025 and will be used to inform further clinical development of SRK-439, a novel investigational myostatin inhibitor for the treatment of obesity. 

[Apitegromab](https://investors.scholarrock.com/static-files/c1e0efad-c0d2-4890-bed4-19e2ec3a1522) targets and selectively inhibits myostatin, allowing patients to build muscle, as the company has proven in its SMA studies. These analyses have also deemed the medication as tolerable.

With previous studies that evaluated the drug in other disease areas, the company launched the proof-of-concept study to assess its impact on obesity for patients using GLP-1 drugs.

“We're applying apitegromab map into a proof-of-concept study in obesity in combination with the GLP-1 receptor agonist. For five years, we've been deeply trying to understand the role, and we've shown, again in our nonclinical work, that sets the stage for the clinical studies, that when we combine [apitegromab] with semaglutide in these clinical models, we preserve lean muscle and enhance glucose metabolism.”

“Our key question for this proof of concept is, does our very selective and specific strategy do that?” Backstrom continued. “The way to show that, the gold standard, is something called DEXA scans. It was introduced to measure bone mineral density.”

Using DEXA scans in the proof-of-concept study will help Scholar Rock quantify the amount of fat loss and muscle loss, which will be one of the study’s primary endpoints.

The other insight the company hopes to gain from this study is an understanding of the benefit–risk of this drug.

“We’ve had highly effective weight loss therapies over the years. The problem is that the risks of those effective therapies outweighed the benefits,” noted Backstrom. For example, amphetamines also aid in weight loss, but they come with intense risks.

While they hypothesize that their myostatin targeting is selective and will not bring about additional toxicities, Scholar Rock hopes the study supports that.

“Safety will be important in our proof of concept because it'll be a randomized study, and we'll be able to look at the profile for the GL-1s. Then we'll be able to show our program side by side, and it's our view from our current data that we will not bring any additional problematic issues,” Backstrom added. “Tolerability will be just what you'd expect. And if anything, if we [expect] an additive effect.”

As the study progresses, the company will continue to monitor how apitegromab works alongside GLP-1 drugs to maintain muscle mass during weight loss.

_Editor's Note: This article has been edited to clarify the study's role in  SRK-439 research._

#### __Next Steps

  * [Exploring and Managing GLP-1 Receptor Agonists in Weight Loss](https://www.techtarget.com/pharmalifesciences/answer/Exploring-and-Managing-GLP-1-Receptor-Agonists-in-Weight-Loss)
  * [Guiding Obesity Management by Understanding Weight Loss Drugs](https://www.techtarget.com/pharmalifesciences/feature/Guiding-Obesity-Management-by-Understanding-Weight-Loss-Drugs)



####  __Dig Deeper on Clinical trials and evidence

  * ##### [Weighing employer GLP-1 coverage considerations ![KelseyWaddill](https://www.techtarget.com/rms/onlineImages/waddill_kelsey.jpg) By: Kelsey Waddill ](https://www.techtarget.com/healthcarepayers/feature/Weighing-employer-GLP-1-coverage-considerations)
  * ##### [FDA approves Zepbound for obstructive sleep apnea ![VeronicaSalib](https://www.techtarget.com/rms/onlineImages/salib_veronica.jpg) By: Veronica Salib ](https://www.techtarget.com/pharmalifesciences/news/366617602/FDA-approves-Zepbound-for-obstructive-sleep-apnea)
  * ##### [Zepbound outperforms Wegovy in weight loss clinical trial ![VeronicaSalib](https://www.techtarget.com/rms/onlineImages/salib_veronica.jpg) By: Veronica Salib ](https://www.techtarget.com/pharmalifesciences/news/366616720/Zepbound-outperforms-Wegovy-in-weight-loss-clinical-trial)
  * ##### [Anticipating the healthcare reach of GLP-1 receptor agonists ![VeronicaSalib](https://www.techtarget.com/rms/onlineImages/salib_veronica.jpg) By: Veronica Salib ](https://www.techtarget.com/pharmalifesciences/feature/Anticipating-the-healthcare-reach-of-GLP-1-receptor-agonists)



#### __Related Q &A; from [Veronica Salib](https://www.techtarget.com/contributor/Veronica-Salib)

##### [Could Roche’s malaria test help address the national blood shortage?](https://www.techtarget.com/pharmalifesciences/answer/Could-Roches-malaria-test-help-address-the-national-blood-shortage)

Strategies for ending the national blood shortage may include expanding the donor pool, rationing, and diagnostic tests.  [Continue Reading](https://www.techtarget.com/pharmalifesciences/answer/Could-Roches-malaria-test-help-address-the-national-blood-shortage)

##### [Understanding the widespread impacts of pharmacy deserts](https://www.techtarget.com/pharmalifesciences/answer/Understanding-the-widespread-impacts-of-pharmacy-deserts)

Pharmacy deserts, perpetuated by multiple factors, have significant implications for patient care and public health.  [Continue Reading](https://www.techtarget.com/pharmalifesciences/answer/Understanding-the-widespread-impacts-of-pharmacy-deserts)

##### [Effectively incorporating AI into drug research, development](https://www.techtarget.com/pharmalifesciences/answer/Effectively-incorporating-AI-into-drug-research-development)

A recent report from Accenture analyzes the value and impact AI can have on drug research and development.  [Continue Reading](https://www.techtarget.com/pharmalifesciences/answer/Effectively-incorporating-AI-into-drug-research-development)

__Sponsored News

  * [Formulating a specialty drug management playbook using expert insights](https://www.techtarget.com/pharmalifesciences/Optum/Formulating-a-specialty-drug-management-playbook-using-expert-insights) -Optum Specialty Fusion
  * [Optimizing Specialty Drug Management: Early Case Study Findings](https://www.techtarget.com/pharmalifesciences/Optum/Optimizing-Specialty-Drug-Management-Early-Case-Study-Findings) -Optum Specialty Fusion
  * [Exploring Trends Shaping the Future of Specialty Pharmacy](https://www.techtarget.com/pharmalifesciences/Optum/Exploring-Trends-Shaping-the-Future-of-Specialty-Pharmacy) -Optum Specialty Fusion



__Related Expert Q &A;

  * [Exploring and Managing GLP-1 Receptor Agonists in ...](https://www.techtarget.com/pharmalifesciences/answer/Exploring-and-Managing-GLP-1-Receptor-Agonists-in-Weight-Loss) - Pharma Life Sciences
  * [Are compounded “DIY” peptides the answer to the GLP-1...](https://www.techtarget.com/pharmalifesciences/answer/Are-compounded-DIY-peptides-the-answer-to-the-GLP-1-shortage) - Pharma Life Sciences
  * [Analyzing 2023 Drug List Price Increases by ...](https://www.techtarget.com/pharmalifesciences/answer/Analyzing-2023-Drug-List-Price-Increases-by-Pharmaceutical-Companies) - Pharma Life Sciences



Latest TechTarget resources

  * Healthtech Analytics ____
  * Healthcare Payers ____
  * Health IT ____
  * Healthtech Security ____



[ xtelligent Healthtech Analytics](https://www.techtarget.com/healthtechanalytics/)

  * __[How health systems are building clinician trust in AI](https://www.techtarget.com/healthtechanalytics/feature/How-health-systems-are-building-clinician-trust-in-AI)

Mayo Clinic, Vanderbilt University Medical Center and Duke Health leaders highlighted strategies to foster trust in AI tools and ...

  * __[PCPs seek additional training to fully trust healthcare AI](https://www.techtarget.com/healthtechanalytics/news/366619696/PCPs-seek-additional-training-to-fully-trust-healthcare-AI)

New survey data show that while using healthcare AI is common in primary care, clinicians desire additional training to fully ...

  * __[Electronic frailty index predicts risk of adverse outcomes](https://www.techtarget.com/healthtechanalytics/news/366619613/Electronic-frailty-index-predicts-risk-of-adverse-outcomes)

Mass General Brigham's electronic frailty index analyzes EHR data to assess patient frailty, helping predict adverse outcomes and...




[ xtelligent Healthcare Payers](https://www.techtarget.com/healthcarepayers/)

  * __[What are the implications of Medicaid per capita caps?](https://www.techtarget.com/healthcarepayers/news/366619739/What-are-the-implications-of-Medicaid-per-capita-caps)

Medicaid per capita caps would decrease federal spending, creating a choice between increased state spending and enrollee ...

  * __[How companies find solutions to employer GLP-1 coverage](https://www.techtarget.com/healthcarepayers/feature/How-companies-find-solutions-to-employer-GLP-1-coverage)

Employer GLP-1 coverage has serious cost barriers, but some companies are turning to technology vendors to provide a ...

  * __[Employers seek healthcare price transparency to control costs](https://www.techtarget.com/healthcarepayers/feature/Employers-seek-healthcare-price-transparency-to-control-costs)

Navigate rising costs by leveraging healthcare price transparency, direct provider contracts and data access, despite ongoing ...




[ xtelligent Health IT and EHR](https://www.techtarget.com/searchhealthit/)

  * __[Oracle Health applies for TEFCA QHIN designation](https://www.techtarget.com/searchhealthit/news/366619566/Oracle-Health-applies-for-TEFCA-QHIN-designation)

If approved, Oracle Health will be the ninth TEFCA qualified health information network (QHIN), joining Epic, Health Gorilla, ...

  * __[Ambient scribing reduces cognitive burden of documentation](https://www.techtarget.com/searchhealthit/news/366619518/Ambient-scribing-reduces-cognitive-burden-of-documentation)

While ambient scribing shows promise for clinical documentation efficiency, the technology may be more suitable for certain ...

  * __[Early lessons on SDOH data integration across health plans](https://www.techtarget.com/searchhealthit/podcast/Early-lessons-on-SDOH-data-integration-across-health-plans)

A new NCQA study found that while SDOH data collection is feasible, health plans face various challenges ranging from siloed data...




[ xtelligent Healthtech Security](https://www.techtarget.com/healthtechsecurity/)

  * __[MGMA, CHIME ask Trump to rescind proposed HIPAA Security Rule](https://www.techtarget.com/healthtechsecurity/news/366619712/MGMA-CHIME-ask-Trump-to-rescind-proposed-HIPAA-Security-Rule)

Several industry groups signed a letter to the Trump administration asking it to rescind the proposed HIPAA Security Rule updates...

  * __[How benchmarking data can improve medical device security](https://www.techtarget.com/healthtechsecurity/feature/How-benchmarking-data-can-improve-medical-device-security)

Participation in benchmarking efforts can help medical device manufacturers better understand their security maturity and build ...

  * __[OCR: Warby Parker to pay $1.5M penalty for violating HIPAA](https://www.techtarget.com/healthtechsecurity/news/366619430/OCR-Warby-Parker-to-pay-15M-penalty-for-violating-HIPAA)

Warby Parker faces a $1.5 million penalty for violating HIPAA, OCR determined after launching an investigation into a 2018 ...




  * [About Us](https://www.techtarget.com/editorial/)
  * [Editorial Ethics Policy](https://www.techtarget.com/techtarget-editorial-ethics-policy/)
  * [Meet The Editors](https://www.techtarget.com/editorial-contacts/)
  * [Contact Us](https://www.techtarget.com/contact-us/)
  * [Privacy Policy](https://www.techtarget.com/privacy-policy/)


  * [Advertisers](https://www.techtarget.com/for-advertisers/)
  * [Business Partners](https://www.techtarget.com/partner-with-us/)
  * [Media Kit](https://www.techtarget.com/wp-content/uploads/2023/09/TechTarget-Media-Kit-Handout-with-product-descriptions.pdf)
  * [Corporate Site](https://www.techtarget.com)
  * [Contributors](https://www.techtarget.com/pharmalifesciences/contributors)


  * [Reprints](http://reprints.ygsgroup.com/m/techtarget)
  * [Answers](https://www.techtarget.com/pharmalifesciences/answers)
  * [Features](https://www.techtarget.com/pharmalifesciences/features)
  * [News](https://www.techtarget.com/news/)



All Rights Reserved,  [Copyright 2024 - 2025](https://www.techtarget.com/pharmalifesciences/about/copyright), TechTarget  
  
[Privacy Policy](https://www.techtarget.com/privacy-policy/)   
Cookie Preferences    
Cookie Preferences    
[Do Not Sell or Share My Personal Information](https://techtarget.zendesk.com/hc/en-us/requests/new?ticket_form_id=360004852434)

Close


url: https://www.mdpi.com/2075-1729/14/6/690
scrape_date: 2025-02-28T09:09:39.871798
content_type: markdown
hash: 1f7ac8092de759bad092786e59b1b2b7b63597ca88a7102efe0554daf7bf0fac
title:
Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis

content:
__

Next Article in Journal  


[Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort](/2075-1729/14/6/689)

__

Previous Article in Journal  


[Microbiome Modulation in Acne Patients and Clinical Correlations](/2075-1729/14/6/688)

## Journals

[Active Journals](/about/journals) [Find a Journal](/about/journalfinder) [Journal Proposal](/about/journals/proposal) [Proceedings Series](/about/proceedings)

## [Topics ](/topics)

## Information

[For Authors](/authors) [For Reviewers](/reviewers) [For Editors](/editors) [For Librarians](/librarians) [For Publishers](/publishing_services) [For Societies](/societies) [For Conference Organizers](/conference_organizers)

[Open Access Policy](/openaccess) [Institutional Open Access Program](/ioap) [Special Issues Guidelines](/special_issues_guidelines) [Editorial Process](/editorial_process) [Research and Publication Ethics](/ethics) [Article Processing Charges](/apc) [Awards](/awards) [Testimonials](/testimonials)

## [Author Services ](/authors/english)

## Initiatives

[Sciforum](https://sciforum.net) [MDPI Books](https://www.mdpi.com/books) [Preprints.org](https://www.preprints.org) [Scilit](https://www.scilit.com) [SciProfiles](https://sciprofiles.com) [Encyclopedia](https://encyclopedia.pub) [JAMS](https://jams.pub) [Proceedings Series](/about/proceedings)

## About

[Overview](/about) [Contact](/about/contact) [Careers](https://careers.mdpi.com) [News](/about/announcements) [Press](/about/press) [Blog](http://blog.mdpi.com/)

[Sign In / Sign Up](/user/login)

## Notice

You can make submissions to other journals [here](https://susy.mdpi.com/user/manuscripts/upload). 

_clear_

## Notice

You are accessing a machine-readable page. In order to be human-readable, please install an RSS reader. 

Continue Cancel

_clear_

All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to <https://www.mdpi.com/openaccess>. 

Feature papers represent the most advanced research with significant potential for high impact in the field. A Feature Paper should be a substantial original Article that involves several techniques or approaches, provides an outlook for future research directions and describes possible research applications. 

Feature papers are submitted upon individual invitation or recommendation by the scientific editors and must receive positive feedback from the reviewers. 

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal. 

Original Submission Date Received: . 

You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled. 

[ ![](https://pub.mdpi-res.com/img/design/mdpi-pub-logo-black-small1.svg?da3a8dcae975a41c?1740558760) ](/)

_clear_ [ _zoom_out_map_ ](/toggle_desktop_layout_cookie "Toggle desktop layout") _search_ _menu_

[ ![](https://pub.mdpi-res.com/img/design/mdpi-pub-logo-black-small1.svg?da3a8dcae975a41c?1740558760) ](/)

  * [Journals](/about/journals)
    *       * [ Active Journals ](/about/journals)
      * [ Find a Journal ](/about/journalfinder)
      * [ Journal Proposal ](/about/journals/proposal)
      * [ Proceedings Series ](/about/proceedings)

  * [Topics](/topics)
  * [Information](/authors)
    *       * [For Authors](/authors)
      * [For Reviewers](/reviewers)
      * [For Editors](/editors)
      * [For Librarians](/librarians)
      * [For Publishers](/publishing_services)
      * [For Societies](/societies)
      * [For Conference Organizers](/conference_organizers)

      * [Open Access Policy](/openaccess)
      * [Institutional Open Access Program](/ioap)
      * [Special Issues Guidelines](/special_issues_guidelines)
      * [Editorial Process](/editorial_process)
      * [Research and Publication Ethics](/ethics)
      * [Article Processing Charges](/apc)
      * [Awards](/awards)
      * [Testimonials](/testimonials)

  * [Author Services](/authors/english)
  * [Initiatives](/about/initiatives)
    *       * [ Sciforum ](https://sciforum.net)
      * [ MDPI Books ](https://www.mdpi.com/books)
      * [ Preprints.org ](https://www.preprints.org)
      * [ Scilit ](https://www.scilit.com)
      * [ SciProfiles ](https://sciprofiles.com)
      * [ Encyclopedia ](https://encyclopedia.pub)
      * [ JAMS ](https://jams.pub)
      * [ Proceedings Series ](/about/proceedings)

  * [About](/about)
    *       * [ Overview ](/about)
      * [ Contact ](/about/contact)
      * [ Careers ](https://careers.mdpi.com)
      * [ News ](/about/announcements)
      * [ Press ](/about/press)
      * [ Blog ](http://blog.mdpi.com/)




[Sign In / Sign Up](/user/login) [Submit](            https://susy.mdpi.com/user/manuscripts/upload?journal=life
    )

 

 

Search for Articles:

Title / Keyword

Author / Affiliation / Email

Journal

All Journals Acoustics  Acta Microbiologica Hellenica (AMH)  Actuators  Adhesives  Administrative Sciences  Adolescents  Advances in Respiratory Medicine (ARM)  Aerobiology  Aerospace  Agriculture  AgriEngineering  Agrochemicals  Agronomy  AI  AI Sensors  Air  Algorithms  Allergies  Alloys  Analytica  Analytics  Anatomia  Anesthesia Research  Animals  Antibiotics  Antibodies  Antioxidants  Applied Biosciences  Applied Mechanics  Applied Microbiology  Applied Nano  Applied Sciences  Applied System Innovation (ASI)  AppliedChem  AppliedMath  Aquaculture Journal  Architecture  Arthropoda  Arts  Astronomy  Atmosphere  Atoms  Audiology Research  Automation  Axioms  Bacteria  Batteries  Behavioral Sciences  Beverages  Big Data and Cognitive Computing (BDCC)  BioChem  Bioengineering  Biologics  Biology  Biology and Life Sciences Forum  Biomass  Biomechanics  BioMed  Biomedicines  BioMedInformatics  Biomimetics  Biomolecules  Biophysica  Biosensors  Biosphere  BioTech  Birds  Blockchains  Brain Sciences  Buildings  Businesses  C (Journal of Carbon Research)  Cancers  Cardiogenetics  Catalysts  Cells  Ceramics  Challenges  ChemEngineering  Chemistry  Chemistry Proceedings  Chemosensors  Children  Chips  CivilEng  Clean Technologies (Clean Technol.)  Climate  Clinical and Translational Neuroscience (CTN)  Clinical Bioenergetics  Clinics and Practice  Clocks & Sleep  Coasts  Coatings  Colloids and Interfaces  Colorants  Commodities  Complexities  Complications  Compounds  Computation  Computer Sciences & Mathematics Forum  Computers  Condensed Matter  Conservation  Construction Materials  Corrosion and Materials Degradation (CMD)  Cosmetics  COVID  Craniomaxillofacial Trauma & Reconstruction (CMTR)  Crops  Cryo  Cryptography  Crystals  Current Issues in Molecular Biology (CIMB)  Current Oncology  Dairy  Data  Dentistry Journal  Dermato  Dermatopathology  Designs  Diabetology  Diagnostics  Dietetics  Digital  Disabilities  Diseases  Diversity  DNA  Drones  Drugs and Drug Candidates (DDC)  Dynamics  Earth  Ecologies  Econometrics  Economies  Education Sciences  Electricity  Electrochem  Electronic Materials  Electronics  Emergency Care and Medicine  Encyclopedia  Endocrines  Energies  Energy Storage and Applications (ESA)  Eng  Engineering Proceedings  Entropy  Environmental and Earth Sciences Proceedings  Environments  Epidemiologia  Epigenomes  European Burn Journal (EBJ)  European Journal of Investigation in Health, Psychology and Education (EJIHPE)  Fermentation  Fibers  FinTech  Fire  Fishes  Fluids  Foods  Forecasting  Forensic Sciences  Forests  Fossil Studies  Foundations  Fractal and Fractional (Fractal Fract)  Fuels  Future  Future Internet  Future Pharmacology  Future Transportation  Galaxies  Games  Gases  Gastroenterology Insights  Gastrointestinal Disorders  Gastronomy  Gels  Genealogy  Genes  Geographies  GeoHazards  Geomatics  Geometry  Geosciences  Geotechnics  Geriatrics  Glacies  Gout, Urate, and Crystal Deposition Disease (GUCDD)  Grasses  Green Health  Hardware  Healthcare  Hearts  Hemato  Hematology Reports  Heritage  Histories  Horticulturae  Hospitals  Humanities  Humans  Hydrobiology  Hydrogen  Hydrology  Hygiene  Immuno  Infectious Disease Reports  Informatics  Information  Infrastructures  Inorganics  Insects  Instruments  Intelligent Infrastructure and Construction  International Journal of Environmental Research and Public Health (IJERPH)  International Journal of Financial Studies (IJFS)  International Journal of Molecular Sciences (IJMS)  International Journal of Neonatal Screening (IJNS)  International Journal of Orofacial Myology and Myofunctional Therapy (IJOM)  International Journal of Plant Biology (IJPB)  International Journal of Topology  International Journal of Translational Medicine (IJTM)  International Journal of Turbomachinery, Propulsion and Power (IJTPP)  International Medical Education (IME)  Inventions  IoT  ISPRS International Journal of Geo-Information (IJGI)  J  Journal of Ageing and Longevity (JAL)  Journal of Cardiovascular Development and Disease (JCDD)  Journal of Clinical & Translational Ophthalmology (JCTO)  Journal of Clinical Medicine (JCM)  Journal of Composites Science (J. Compos. Sci.)  Journal of Cybersecurity and Privacy (JCP)  Journal of Dementia and Alzheimer's Disease (JDAD)  Journal of Developmental Biology (JDB)  Journal of Experimental and Theoretical Analyses (JETA)  Journal of Eye Movement Research (JEMR)  Journal of Functional Biomaterials (JFB)  Journal of Functional Morphology and Kinesiology (JFMK)  Journal of Fungi (JoF)  Journal of Imaging (J. Imaging)  Journal of Intelligence (J. Intell.)  Journal of Low Power Electronics and Applications (JLPEA)  Journal of Manufacturing and Materials Processing (JMMP)  Journal of Marine Science and Engineering (JMSE)  Journal of Market Access & Health Policy (JMAHP)  Journal of Mind and Medical Sciences (JMMS)  Journal of Molecular Pathology (JMP)  Journal of Nanotheranostics (JNT)  Journal of Nuclear Engineering (JNE)  Journal of Otorhinolaryngology, Hearing and Balance Medicine (JOHBM)  Journal of Parks  Journal of Personalized Medicine (JPM)  Journal of Pharmaceutical and BioTech Industry (JPBI)  Journal of Respiration (JoR)  Journal of Risk and Financial Management (JRFM)  Journal of Sensor and Actuator Networks (JSAN)  Journal of the Oman Medical Association (JOMA)  Journal of Theoretical and Applied Electronic Commerce Research (JTAER)  Journal of Vascular Diseases (JVD)  Journal of Xenobiotics (JoX)  Journal of Zoological and Botanical Gardens (JZBG)  Journalism and Media  Kidney and Dialysis  Kinases and Phosphatases  Knowledge  LabMed  Laboratories  Land  Languages  Laws  Life  Limnological Review  Lipidology  Liquids  Literature  Livers  Logics  Logistics  Lubricants  Lymphatics  Machine Learning and Knowledge Extraction (MAKE)  Machines  Macromol  Magnetism  Magnetochemistry  Marine Drugs  Materials  Materials Proceedings  Mathematical and Computational Applications (MCA)  Mathematics  Medical Sciences  Medical Sciences Forum  Medicina  Medicines  Membranes  Merits  Metabolites  Metals  Meteorology  Methane  Methods and Protocols (MPs)  Metrics  Metrology  Micro  Microbiology Research  Micromachines  Microorganisms  Microplastics  Microwave  Minerals  Mining  Modelling  Modern Mathematical Physics  Molbank  Molecules  Multimedia  Multimodal Technologies and Interaction (MTI)  Muscles  Nanoenergy Advances  Nanomanufacturing  Nanomaterials  NDT  Network  Neuroglia  Neurology International  NeuroSci  Nitrogen  Non-Coding RNA (ncRNA)  Nursing Reports  Nutraceuticals  Nutrients  Obesities  Oceans  Onco  Optics  Oral  Organics  Organoids  Osteology  Oxygen  Parasitologia  Particles  Pathogens  Pathophysiology  Pediatric Reports  Pets  Pharmaceuticals  Pharmaceutics  Pharmacoepidemiology  Pharmacy  Philosophies  Photochem  Photonics  Phycology  Physchem  Physical Sciences Forum  Physics  Physiologia  Plants  Plasma  Platforms  Pollutants  Polymers  Polysaccharides  Populations  Poultry  Powders  Proceedings  Processes  Prosthesis  Proteomes  Psychiatry International  Psychoactives  Psychology International  Publications  Purification  Quantum Beam Science (QuBS)  Quantum Reports  Quaternary  Radiation  Reactions  Real Estate  Receptors  Recycling  Regional Science and Environmental Economics (RSEE)  Religions  Remote Sensing  Reports  Reproductive Medicine (Reprod. Med.)  Resources  Rheumato  Risks  Robotics  Ruminants  Safety  Sci  Scientia Pharmaceutica (Sci. Pharm.)  Sclerosis  Seeds  Sensors  Separations  Sexes  Signals  Sinusitis  Smart Cities  Social Sciences  Société Internationale d’Urologie Journal (SIUJ)  Societies  Software  Soil Systems  Solar  Solids  Spectroscopy Journal  Sports  Standards  Stats  Stresses  Surfaces  Surgeries  Surgical Techniques Development  Sustainability  Sustainable Chemistry  Symmetry  SynBio  Systems  Targets  Taxonomy  Technologies  Telecom  Textiles  Thalassemia Reports  Therapeutics  Thermo  Time and Space  Tomography  Tourism and Hospitality  Toxics  Toxins  Transplantology  Trauma Care  Trends in Higher Education  Tropical Medicine and Infectious Disease (TropicalMed)  Universe  Urban Science  Uro  Vaccines  Vehicles  Venereology  Veterinary Sciences  Vibration  Virtual Worlds  Viruses  Vision  Waste  Water  Wild  Wind  Women  World  World Electric Vehicle Journal (WEVJ)  Youth  Zoonotic Diseases 

Article Type

All Article Types Article Review Communication Editorial Abstract Book Review Brief Communication Brief Report Case Report Clinicopathological Challenge Comment Commentary Concept Paper Conference Report Correction Creative Data Descriptor Discussion Entry Essay Expression of Concern Extended Abstract Field Guide Giants in Urology Guidelines Hypothesis Interesting Images Letter New Book Received Obituary Opinion Perspective Proceeding Paper Project Report Protocol Registered Report Reply Retraction Short Note Study Protocol Systematic Review Technical Note Tutorial Urology around the World Viewpoint

 

 

Advanced Search

 

Section

Special Issue

Volume

Issue

Number

Page

 

Logical OperatorOperator

AND OR

Search Text

Search Type

All fields Title Abstract Keywords Authors Affiliations Doi Full Text References

 

_add_circle_outline_

_remove_circle_outline_

 

 

[Journals](/about/journals)

[Life](/journal/life)

[Volume 14](/2075-1729/14)

[Issue 6](/2075-1729/14/6)

10.3390/life14060690

[ ![life-logo](https://pub.mdpi-res.com/img/journals/life-logo.png?8600e93ff98dbf14) ](/journal/life)

[ Submit to this Journal ](https://susy.mdpi.com/user/manuscripts/upload?form%5Bjournal_id%5D%3D51) [ Review for this Journal ](https://susy.mdpi.com/volunteer/journals/review) [ Propose a Special Issue ](/journalproposal/sendproposalspecialissue/life)

► ▼ Article Menu 

## Article Menu

  * Academic Editors

![](https://pub.mdpi-res.com/bundles/mdpisciprofileslink/img/unknown-user.png?1740558760) Changwon Park

[![](/profiles/210347/thumb/Fabrizio_Montecucco.png)Fabrizio Montecucco](https://sciprofiles.com/profile/210347?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name)

  * [Subscribe SciFeed](/2075-1729/14/6/690/scifeed_display)
  * Recommended Articles
  * Related Info Links

    * [PubMed/Medline](http://www.ncbi.nlm.nih.gov/sites/entrez/38929672)
    * [Google Scholar](https://scholar.google.com/scholar?q=Effect%20of%20GLP-1RA%20Treatment%20on%20Adhesion%20Molecules%20and%20Monocyte%20Chemoattractant%20Protein-1%20in%20Diabetic%20Patients%20with%20Atherosclerosis)

  * More by Authors Links

    * on DOAJ

      * [Hachuła, M.](http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22Marcin%20Hachu%C5%82a%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D)
      *       * [Basiak, M.](http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22Marcin%20Basiak%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D)
      *       * [Kosowski, M.](http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22Micha%C5%82%20Kosowski%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D)
      *       * [Okopień, B.](http://doaj.org/search/articles?source=%7B%22query%22%3A%7B%22query_string%22%3A%7B%22query%22%3A%22%5C%22Bogus%C5%82aw%20Okopie%C5%84%5C%22%22%2C%22default_operator%22%3A%22AND%22%2C%22default_field%22%3A%22bibjson.author.name%22%7D%7D%7D)
      *     * on Google Scholar

      * [Hachuła, M.](https://scholar.google.com/scholar?q=Marcin%20Hachu%C5%82a)
      *       * [Basiak, M.](https://scholar.google.com/scholar?q=Marcin%20Basiak)
      *       * [Kosowski, M.](https://scholar.google.com/scholar?q=Micha%C5%82%20Kosowski)
      *       * [Okopień, B.](https://scholar.google.com/scholar?q=Bogus%C5%82aw%20Okopie%C5%84)
      *     * on PubMed

      * [Hachuła, M.](http://www.pubmed.gov/?cmd=Search&term=Marcin%20Hachu%C5%82a)
      *       * [Basiak, M.](http://www.pubmed.gov/?cmd=Search&term=Marcin%20Basiak)
      *       * [Kosowski, M.](http://www.pubmed.gov/?cmd=Search&term=Micha%C5%82%20Kosowski)
      *       * [Okopień, B.](http://www.pubmed.gov/?cmd=Search&term=Bogus%C5%82aw%20Okopie%C5%84)
      * 
/ajax/scifeed/subscribe

Article Views

Citations -

  * Table of Contents




Altmetric _share_ Share _announcement_ Help [ _format_quote_ Cite ](javascript:void\(0\);) [ _question_answer_ Discuss in SciProfiles ](https://sciprofiles.com/discussion-groups/public/10.3390/life14060690?utm_source=mpdi.com&utm_medium=publication&utm_campaign=discuss_in_sciprofiles "Discuss in Sciprofiles")

## Need Help?

### Support

Find support for a specific problem in the support section of our website. 

[ Get Support ](/about/contactform)

### Feedback

Please let us know what you think of our products and services. 

[ Give Feedback ](/feedback/send)

### Information

Visit our dedicated information section to learn more about MDPI. 

[ Get Information ](/authors)

_clear_

## JSmol Viewer

_clear_

_first_page_

[ __Download PDF](/2075-1729/14/6/690/pdf?version=1716881835)

_settings_

[ Order Article Reprints ](/2075-1729/14/6/690/reprints)

Font Type: 

_Arial_ _Georgia_ _Verdana_

Font Size:

Aa Aa Aa

Line Spacing:

__ __ __

Column Width:

__ __ __

Background:

__

__

__

Open AccessArticle

#  Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis 

by 

Marcin Hachuła

![](/bundles/mdpisciprofileslink/img/unknown-user.png)Marcin Hachuła

[ SciProfiles ](https://sciprofiles.com/profile/1912315?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name)[ Scilit ](https://scilit.com/scholars?q=Marcin%20Hachu%C5%82a)[ Preprints.org ](https://www.preprints.org/search?search1=Marcin%20Hachu%C5%82a&field1=authors)[ Google Scholar ](https://scholar.google.com/scholar?q=Marcin%20Hachu%C5%82a)

[__](/cdn-cgi/l/email-protection#6e410d000a430d09074102410b030f0702431e1c011a0b0d1a0701004d5e5e5e0d580a5f085e0b5e5a5e5d5a5d5e5b5e0d5e0b5e5b5f565e5f5e0d5c0a5e0f5e5e5e0d5e5a5e5f5a5d5e0b5e5c5e5e)[![](https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1740558760)](https://orcid.org/0000-0001-9023-676X),

Marcin Basiak

![](/bundles/mdpisciprofileslink/img/unknown-user.png)Marcin Basiak

[ SciProfiles ](https://sciprofiles.com/profile/1413306?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name)[ Scilit ](https://scilit.com/scholars?q=Marcin%20Basiak)[ Preprints.org ](https://www.preprints.org/search?search1=Marcin%20Basiak&field1=authors)[ Google Scholar ](https://scholar.google.com/scholar?q=Marcin%20Basiak)

*[__](/cdn-cgi/l/email-protection#644b070a004907030d4b084b0109050d084914160b100107100d0b0a475454540252005407550154505407545256005501555c54545057545c545d555c505755005455)[![](https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1740558760)](https://orcid.org/0000-0003-0674-5612),

Michał Kosowski

![](/bundles/mdpisciprofileslink/img/unknown-user.png)Michał Kosowski

[ SciProfiles ](https://sciprofiles.com/profile/1475210?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name)[ Scilit ](https://scilit.com/scholars?q=Micha%C5%82%20Kosowski)[ Preprints.org ](https://www.preprints.org/search?search1=Micha%C5%82%20Kosowski&field1=authors)[ Google Scholar ](https://scholar.google.com/scholar?q=Micha%C5%82%20Kosowski)

[__](/cdn-cgi/l/email-protection#eac589848ec7898d83c586c58f878b8386c79a98859e8f899e838584c9dadadadcdc8edad8db8fdad8db8bdb8fdadcdaded88edb8fdbd2dadaded9dad2dad3dbd2ded9db8edadb)[![](https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1740558760)](https://orcid.org/0000-0003-2597-463X)and

Bogusław Okopień

![](/bundles/mdpisciprofileslink/img/unknown-user.png)Bogusław Okopień

[ SciProfiles ](https://sciprofiles.com/profile/1541695?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name)[ Scilit ](https://scilit.com/scholars?q=Bogus%C5%82aw%20Okopie%C5%84)[ Preprints.org ](https://www.preprints.org/search?search1=Bogus%C5%82aw%20Okopie%C5%84&field1=authors)[ Google Scholar ](https://scholar.google.com/scholar?q=Bogus%C5%82aw%20Okopie%C5%84)

[__](/cdn-cgi/l/email-protection#ddf2beb3b9f0bebab4f2b1f2b8b0bcb4b1f0adafb2a9b8bea9b4b2b3feedededb9ebefede4edb9ecefedbfedeaedbeefefecececeaedbbe9beedeaedebeceae9beecefedb8)[![](https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1740558760)](https://orcid.org/0000-0001-7228-2906)

Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland

*

Author to whom correspondence should be addressed. 

_Life_ **2024** , _14_(6), 690; <https://doi.org/10.3390/life14060690>

Submission received: 12 April 2024 / Revised: 19 May 2024 / Accepted: 24 May 2024 / Published: 28 May 2024

(This article belongs to the Section [Physiology and Pathology](/journal/life/sections/Physiology_and_Pathology))  


Download _keyboard_arrow_down_

[Download PDF](/2075-1729/14/6/690/pdf?version=1716881835)   
Download PDF with Cover   
Download XML   
[Download Epub](/2075-1729/14/6/690/epub)   


Browse Figures

[ ](https://pub.mdpi-res.com/life/life-14-00690/article_deploy/html/images/life-14-00690-g001.png?1716881985 "
                        <strong>Figure 1</strong><br/>
                                                    <p>Concentration of ICAM-1 in study group before and after intervention.</p>
                                                ") [ ](https://pub.mdpi-res.com/life/life-14-00690/article_deploy/html/images/life-14-00690-g002.png?1716881986 "
                        <strong>Figure 2</strong><br/>
                                                    <p>Concentration of L-selectin in study group before and after intervention.</p>
                                                ") [ ](https://pub.mdpi-res.com/life/life-14-00690/article_deploy/html/images/life-14-00690-g003.png?1716881987 "
                        <strong>Figure 3</strong><br/>
                                                    <p>Concentration of MCP-1 in study group before and after intervention.</p>
                                                ")

[Versions Notes](/2075-1729/14/6/690/notes)

## Abstract

**:**

Cardiovascular disease (CVD) remains a prominent cause of global mortality, primarily driven by atherosclerosis. Diabetes mellitus, as a modifiable risk factor, significantly contributes to atherogenesis. Monocyte recruitment to the intima is a critical step in atherosclerotic plaque formation, involving chemokines and adhesion molecules such as selectins, ICAM-1, and MCP-1. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a promising group of drugs for reducing cardiovascular risk in diabetic patients, prompting investigation into their mechanisms of action. This interventional study enrolled 50 diabetes patients with atherosclerotic plaque, administering GLP-1RA for 180 days. Serum concentrations of MCP-1, ICAM-1, and L-selectin were measured before and after treatment. Anthropometric and biochemical parameters were also assessed. GLP-1RA treatment resulted in significant improvements in anthropometric parameters, glycemic control, blood pressure, and biochemical markers of liver steatosis. Biomarker laboratory analysis revealed higher baseline levels of MCP-1, ICAM-1, and L-selectin in diabetic patients with atherosclerotic plaque compared to healthy controls. Following treatment, MCP-1 and L-selectin levels decreased significantly (p < 0.001), while ICAM-1 levels increased (p < 0.001). GLP-1RA treatment in diabetic patients with atherosclerotic plaque leads to favorable changes in serum molecule levels associated with monocyte recruitment to the endothelium. The observed reduction in MCP-1 and L-selectin suggests a potential mechanism underlying GLP-1RA-mediated cardiovascular risk reduction. Further research is warranted to elucidate the precise mechanisms and clinical implications of these findings in diabetic patients with atherosclerosis.

Keywords: 

[atherosclerosis](/search?q=atherosclerosis); [GLP-1 receptor agonist](/search?q=GLP-1+receptor+agonist); [diabetes mellitus](/search?q=diabetes+mellitus); [MCP-1](/search?q=MCP-1); [ICAM-1](/search?q=ICAM-1); [semaglutide](/search?q=semaglutide); [dulaglutide](/search?q=dulaglutide)




##  1\. Introduction

Cardiovascular disease (CVD) remains the foremost global cause of death, as indicated by the Global Burden of Disease (GBD) report, which estimated 19.8 million fatalities attributed to CVD worldwide in 2022 [1]. The main mechanism in the pathogenesis of cardiovascular disease is atherosclerosis [2]. The development of atherosclerosis is multifactorial and consists of numerous non-modifiable and modifiable risk factors. These factors are collectively referred to as cardiovascular risk factors. One of the modifiable risk factors is diabetes mellitus [3]. Excessive blood sugar levels and glycemic fluctuations occurring in diabetes, which result in an increase in the concentration of reactive oxygen species, are strongly associated with atherogenesis, playing a pivotal role not only in triggering the development of atherosclerotic plaques but also exacerbating their advancement and vulnerability [4]. Cardiovascular diseases are the most prevalent cause of mortality and morbidity among individuals with diabetes [5]. A particularly crucial step in the formation of atherosclerotic plaque is the process of monocyte recruitment to the intima. This process includes the rolling, adhesion, activation, and transmigration of monocytes. Numerous chemokines and adhesion molecules participate in these phases [6].

Rolling is facilitated by the selectin family; they are directly involved in atherosclerotic plaque formation [7]. The P and E selectins are expressed by inflamed endothelial cells; their role in the development of atherosclerosis is very well understood [8,9]. In contrast, L-selectin is expressed in the majority of leukocytes and its involvement in this process is still being studied [10].

The binding of selectins with their ligands enables leukocytes to adhere to inflamed sites in the endothelium. In atherosclerotic plaque, chronic inflammation leads to the expression of adhesion molecules and their promotion at the surface of the endothelium. One of these adhesion molecules is intercellular adhesion molecule-1 (ICAM-1), which is engaged in the adhesion of leukocytes and accelerates the migration of these cells into the intima [11]. The involvement of adhesive molecules such as ICAM-1 in cardiovascular diseases is still being studied; however, there is some evidence that their levels are higher in patients with a higher risk of cardiovascular diseases [12,13].

In monocyte transmigration, the predominant chemokine is monocyte chemotactic protein-1 (MCP-1). Its leading role is to recruit monocytes, favoring their transendothelial migration from the circulation to the intima, thus leading to the progression of atherosclerotic plaque [14]. The involvement of MCP-1 in the development of atherosclerosis has been widely recognized and supported by numerous preclinical models in animals, experimental studies on humans with the presence of atherosclerotic plaque in the carotid and coronary arteries, as well as in cases of its instability [15].

Scientists worldwide have recently begun dedicating their attention to a novel class of antidiabetic drugs known as glucagon-like peptide 1 receptor agonists (GLP-1RA). Several important randomized clinical trials, like SUSTAIN, LEADER, REWIND, and PIONEER, have shown that diabetes patients who undergo GLP-1RA therapy have a lower risk of cardiovascular events [16,17]. Recently, both the ESC Guidelines on cardiovascular disease prevention and the ADA have endorsed the use of GLP1-RAs in patients with diabetes and atherosclerotic cardiovascular disease (ASCVD) to mitigate cardiovascular-renal outcomes [18,19].

Regrettably, there is currently an absence of studies that firmly clarify the mechanism by which this group of drugs significantly reduces cardiovascular risk. A hypothesis has arisen claiming that these drugs have an influence on several steps in the process of atherogenesis, which leads to a reduction in cardiovascular events in individuals diagnosed with ASCVD.

The aim of our study was to investigate this hypothesis and verify whether GLP-1 receptor agonists influence the concentrations of chemokines and adhesion molecules involved in the progression of atherosclerotic plaque, such as MCP-1, L-selectin and ICAM-1 in a group of individuals with diabetes mellitus type 2 and confirmed atherosclerotic plaque in the carotid artery.

##  2\. Materials and Methods

The medical experiment was conducted between January 2022 and September 2023. We enrolled 50 participants, aged between 41 and 81 (mean age of 60.7) from a total of 91 patients for our study. All participants were diagnosed with type 2 diabetes mellitus, dyslipidemia and had confirmed the presence of atherosclerotic plaque in the ultrasound Doppler study of carotid arteries. Only those who met the criteria for inclusion and passed very stringent and limited exclusion criteria were eligible for entry into the study. Informed consent was given by each patient in accordance with the Declaration of Helsinki. The information pertaining to the subjects was anonymized. Patients were enrolled at the Department of Internal Medicine and Clinical Pharmacology in Katowice, Poland, as well as through referrals from diabetic outpatient clinics. The study protocol received approval from the Bioethical Committee of the Medical University of Silesia (PCN/CBN/0052/KB1/45/I/22). In a study, 16 patients were given semaglutide and 34 patients were given dulaglutide, both at a standard dose for lowering blood glucose levels. For semaglutide, patients initiated treatment with a dose of 0.25 mg, which was increased to 0.5 mg after 4 weeks, and then to 1 mg after another 4 weeks. Exceptions were made for patients who reported an increase in adverse events at the 1 mg dose; in such cases, the dosage was reduced to 0.5 mg. Additionally, patients who achieved significant improvement in their glycemic profile at the 0.5 mg dose were not eligible for a dose increase. Conversely, for dulaglutide, the target dose was 1.5 mg, with an option to increase to 3 mg in the case of inadequate glycemic control while tolerating adverse events. The medication was administered on a weekly basis, consistently at the same time each day. Throughout the intervention, there were no modifications made to the GLP-1 receptor agonist therapy or any other drugs. The intervention lasted for a period of 26 weeks.

####  2.1. Inclusion and Exclusion Criteria

The requirements for inclusion in the study were as follows: a diagnosis of diabetes mellitus type 2, dyslipidemia, which was defined as having serum total cholesterol (TC) levels above 190 mg/dL, HDL cholesterol lower than 40 mg/dL and triglyceride (TG) levels above 150 mg/dL or were undergoing treatment for dyslipidemia, and the presence of atherosclerotic plaque in the carotid artery. Participants were ineligible for the study if they had the following: recognized type 1 diabetes, exacerbation of chronic heart failure or if they had undergone percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or experienced a stroke within 3 months prior to the study. Additionally, patients with unstable angina were also excluded. The exclusion criteria contained acute and chronic pancreatitis, acute exacerbations of autoimmune disorders, uncontrolled thyroid disease manifested by abnormal TSH values, and any other acute inflammatory processes (including COVID-19 infection) within 4 weeks prior to the study. The reason for exclusion from participation in the study also included acute infections characterized by an increase in CRP value of 5 mg/dL or significant leukocytosis. Additionally, patients with a glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2, classified as chronic kidney disease (CKD) stage G3b, acute and chronic liver diseases (indicated by transaminase levels exceeding 3 times the norm), or a medical history of diagnosed chronic viral hepatitis were also excluded. Lack of informed consent, alcoholism, pregnancy and breastfeeding also resulted in non-inclusion in the study. Following the intervention, a further interview was conducted with all participants. Participants were also disqualified if, in the past 6 months, they had experienced an increase in their level of physical activity; made changes to their dietary habits, for example, if they were consulted by a qualified nutritionist; independently made dietary changes, e.g., adopting a Mediterranean diet or transitioning to a ketogenic diet; altered their treatment plan; or initiated therapy with a new medication that has been shown to impact lipid profile or has a known pleiotropic effect (such as statins, fibrates, ezetimibe, niacin, non-selective beta-blockers, metformin, sodium–glucosium-like transporter 2 (SGLT2) inhibitors, or ursodeoxycholic acid). In addition, patients were excluded if they had a history of coronary or stroke events or if they had undergone a serious infection during the intervention.

####  2.2. Evaluation of Arteriosclerotic Plaque

The carotid arteries were examined in the extracranial region using B-mode and color Doppler ultrasonography with a linear probe at a frequency of 7.5–10 MHz on a Hitachi Aloka F37 ultrasound machine (Kadoma-shi, Japan). To confirm the existence of atherosclerotic plaque in the carotid artery, we used a threshold of a C-IMT complex thickness greater than 1.5 mm or the presence of atherosclerotic plaque.

####  2.3. Anthropometry and Serum Arteriosclerotic Markers Analysis

Measurements were conducted prior to study enrollment and again after 6 months of treatment under the supervision of a physician. Standard techniques were used to assess body weight and height, and body mass index (BMI) was computed in kilograms per square meter (kg/m2). Measurements of waist and hip circumferences were taken at the standard anatomical positions, and the waist-to-hip ratio (WHR) was calculated. The Omron M400 Intelli IT automated device (Mannheim, Germany) was used to measure arterial blood pressure (BP) twice in the sitting position. Researchers estimated the eGFR using the CKD-EPI formula, and they reported the results in mL/min/1.73 m2. Standard laboratory tests were conducted in the accredited laboratory, and venous blood samples were taken after a 12 h fasting period at 8 a.m., both before and after 180 days of treatment. The chemokine and adhesion molecules serum levels were evaluated using enzyme-linked immunosorbent assay (ELISA) kits that were commercially available: MCP-1: (873.030.192, intra-assay CV%—1.8% and inter-assay CV%—3.7%), ICAM-1: (850.540.192, intra-assay CV%—1.93% and inter-assay CV%—6.04%), and L-Selectin: (850.650.192, intra-assay CV%—5.5%), all from Diaclone, (Besancon Cedex, France). To avoid the freeze–thaw effect, each experiment utilized a distinct kit and was conducted on a single sample aliquot.

####  2.4. Statistical Analysis

The data were analyzed using Statistica TIBCO Software Inc. (2017) version 13.3 software (Palo Alto, CA, USA), which was obtained through a license from the Medical University of Silesia in Katowice. We employed the Shapiro–Wilk test to evaluate the normality of the distributions. The values are reported as either means and 95% confidence intervals or medians with Q1–Q3 values. The t-test for independent means and the t-test for dependent means were employed to compare quantitative variables. The U Mann–Whitney test was employed to compare independent variables with a non-normal distribution. We employed the Wilcoxon test to analyze the dependent variables with a normal distribution. In addition, we employed Spearman rank correlation to evaluate the association between variables. We considered a p-value below 0.05 to be statistically significant.

##  3\. Results

####  3.1. Study and Control Group Characteristics

The examination cohort contained 50 participants with an average age of 60.8 ± 9.5 years. Overall, 70% were obese (BMI > 30 kg/m2). The median glycated hemoglobin was 8.75%. All participants had recognized metabolic dysfunction-associated steatotic liver disease (MASLD) and dyslipidemia. The complete list of comorbidities and drugs used by patients is presented in Table 1 and Table 2. At the time of study, the entry median levels of total cholesterol were 166.5 mg/mL, the low-density lipoprotein-cholesterol (LDL-C) was 83 mg/dL, the high-density lipoprotein-cholesterol (HDL-C) was 49.5 mg/dL, the non-HDL was 114 mg/dL and the triglycerides (TG) were 167.9 mg/dL. Respectively, the mean levels of alanine transaminase (ALT) and aspartate transaminase (AST) were 34.4 U/L and 32.5 U/L, gamma-glutamyl transpeptidase (GGTP) was 46.3 U/L, and the mean Fibrosis-4 Index (Fib-4) was 1.5.

The control group consisted of 26 sex-matched healthy volunteers with a mean age of 33.08 ± 5.45 years, including 13 (50%) women. There were no obese individuals. All subjects were not diagnosed with any concomitant diseases. The characteristics and comparison of biochemical parameters between the study and control group are presented in Table 2 and Table 3.

####  3.2. Biochemical Effect after GLP1-RA Treatment

Following treatment in the study group, we noted a statistically significant decrease in anthropometric parameters including BMI (p < 0.001); on average, patients lost over 5.1 kg of weight. A decreased level in fasting glucose and an average reduction of 1.12% in HbA1C (mean: 7.56%) (p < 0.001) were noted. Substantial differences in decreasing blood pressure for SBP (p < 0.001) and DPB (p < 0.001) were noted. In terms of the lipid profile, alterations did not reach statistical significance. However, patients experienced a decrease in LDL fraction, TG, and non-HDL cholesterol, along with an elevation in HDL fraction. Furthermore, we obtained a statistically significant decline in the fibrosis-4 score (FIB-4) (p < 0.001) and De-Ritis Ratio (p < 0.05). The detailed results are presented in Table 3.

####  3.3. Chemokine and Adhesion Molecules Level Analysis

We observed statistically significant higher concentrations of MCP-1, ICAM-1 and L-selectin in patients with diabetes and atherosclerotic plaque before treatment compared to healthy individuals (p < 0.001). After a treatment intervention in our study group, we obtained a statistically significant decrease in MCP-1 and L-selectin (p < 0.001) concentrations, and increased ICAM-1 (p < 0.001). The results are presented in Figure 1, Figure 2 and Figure 3.

####  3.4. Correlation between Changes in Biochemical Parameters and Chemokine and Adhesion Molecules Levels

Additionally, we observed that changes in the concentrations of the studied adhesion molecules and chemokines do not correlate with changes in BMI, weight, lipid profile, or HbA1C value, except for ICAM-1 in terms of glycated hemoglobin. The details of the correlations we investigated are shown in Table 4 and Table 5.

##  4\. Discussion

The presented study was designed to investigate the potential mechanism by which GLP-1 receptor agonists intermediate in the reduction in cardiovascular risk in patients with diabetes and atherosclerotic arterial disease. We demonstrated the beneficial effect of 180 days of therapy on biochemical and anthropometric factors associated with cardiovascular risk, such as body mass, glucose serum level or lipid profile, as well as on the concentration of chemokine and adhesion molecules responsible for recruiting monocytes to the vascular endothelium.

Numerous randomized clinical trials have demonstrated a decrease in cardiovascular risk among diabetic patients receiving GLP-1RA treatment [16,17]. This objective can be attained indirectly through the reduction in other contributing factors or directly by modulating the different molecule levels involved in atherogenesis. Our hypothesis is that GLP1-RA affects chemokine and adhesion molecules involved in monocyte recruitment to the vascular endothelium, which is one of the main pathomechanisms in the development of atherosclerosis.

Cardiovascular risk reduction using GLP1-RA could be achieved indirectly by affecting other well-documented CVD risk factors. The first of these is hyperglycemia. Diabetes type 2 is a significant risk factor for cardiovascular complications, with cardiovascular disease (CVD) being the leading cause of mortality among diabetic patients [20]. Our patients treated with GLP1-RA demonstrated benefits in terms of lower fasting glucose and glycated hemoglobin levels, comparable to those observed in randomized trials [21]. Another crucial factor to consider is dyslipidemia. Patients with diabetes are characterized by abnormalities in the lipid profile, defined as diabetic dyslipidemia, which includes high triglyceride concentrations, a decrease in the HDL cholesterol fraction and the accumulation of very low-density lipoprotein (VLDL), small dense low-density lipoprotein (sdLDL), and chylomicrons. Changes in the lipid profile accelerate atherosclerotic plaque formation [22]. Numerous scientific papers including meta-analyses of studies confirm the positive effect of GLP1-RA treatment on lipid levels in patients with type 2 diabetes. Reductions in total cholesterol, LDL fraction and triglycerides were observed [23]. In our cohort, the changes in lipid profile did not reach statistical significance. However, patients experienced a reduction in LDL, TG, and non-HDL cholesterol fractions, along with an increase in HDL fractions. This may be attributed to the fact that patients in our study group had a pre-existing diagnosis of dyslipidemia and were undergoing treatment with statins (84% individuals); at the baseline, 40% of patients had target LDL cholesterol levels and 44% target triglyceride levels, and following the therapy, there was an increase in this percentage. The absence of statistical significance in lipid profile reduction among diabetic patients was also noted in the LIRAFLAME Randomized Controlled Trial (RCT). Interestingly, in this study, a similar proportion of patients received hypolipemic treatment as in our investigation [24]. Another risk factor is excessive body weight; our patients experienced a weight loss above 5 kg during follow-up. Our findings align with previous studies, and a recently published comprehensive meta-analysis further supports the effectiveness of GLP1-RA in promoting weight reduction [25,26].

In our study, we demonstrated that patients with type 2 diabetes, dyslipidemia and confirmed atherosclerotic plaque in the carotid artery have higher levels of MCP-1, ICAM-1, and L-Selectin, compared to healthy individuals (p < 0.001). Numerous studies corroborate our findings, confirming that these molecules are associated with an increased cardiovascular risk [13,15,27,28].

Within the context of our research, treatment with a GLP-1 receptor agonist for 180 days led to a statistically significant reduction in MCP-1 and L-selectin levels (p < 0.001), accompanied by an increase in ICAM-1 levels (p < 0.001). Moreover, in our study, we performed a Spearman correlation at the same time, showing that the decrease in MCP-1 chemokine levels in our study was not correlated with weight loss, BMI, changes in glycemia or improvements in lipid profile.

Monocyte chemoattractant protein-1 is strongly associated with macrophages localized in the atherosclerotic plaque [29]. During atherosclerotic plaque formation, accumulated oxLDL within the endothelium enhances MCP-1 synthesis, contributing to a macrophage influx to the site of inflammation and atherosclerotic plaque progression, representing one of the key stages of atherogenesis [30]. In experimental animal models, MCP-1 lacking rabbits and mice reduced the development and progression of atherosclerosis [31]. Recent scientific literature highlights MCP-1′s involvement in atherosclerotic plaque instability; elevated levels were observed in patients with vulnerable plaque. This underscores monocyte chemoattractant protein-1 as a promising marker for evaluating the risk of cardiovascular disease stemming from atherosclerosis [32]. On the other hand, a large meta-analysis involving a substantial number of patients has indicated that, even after adjusting for conventional cardiovascular risk factors, caution should be exercised in utilizing MCP-1 levels as predictors of cardiovascular endpoints [33]. Therapeutic interventions aimed at reducing cardiovascular risk involving lifestyle modification, specifically the implementation of the dietary approaches to stop a hypertension (DASH) diet, led to a notable decrease in MCP-1 levels and enhanced the stability of atherosclerotic plaques observed on CT scanning [34]. Also, exercise reduces serum levels of monocyte chemoattractant protein-1 [35]. Drugs known for their well-documented reduction in cardiovascular risk, such as statins, demonstrated a decrease in MCP-1 levels in both cellular and animal experimental models; moreover, this effect was observed to be independent of their lipid-lowering properties [36]. Wesołowska et al., in their study, validated this observation using human peripheral blood cells. Diabetic patients treated with atorvastatin exhibited lower concentrations of MCP-1 compared to patients who did not receive statin treatment [37]. In patients with coronary atherosclerotic disease confirmed using coronary angiography, 3 months of simvastatin treatment led to a statistically significant decrease in MCP-1-induced monocyte migration [38]. Regarding the effect of glucagon-like peptide-1 receptor agonists on monocyte chemoattractant protein-1 concentrations, Bułdak et al. demonstrated that exenatide resulted in a statistically significant reduction in the concentration of this chemokine in human monocytes/macrophages treated with LPS [39]. Similar observations were described in an animal model [40]. Exenatide also reduces MCP-1 levels in patients with type 2 diabetes [41]. In a small randomized controlled trial of ninety-two diabetic patients, a significant decrease in serum MCP-1 levels was achieved after 12 weeks of liraglutide treatment [42]. Mashayekhi et al. made the same observation in their RCT involving patients with obesity and pre-diabetes [43]. In this study, like ours, the decrease in chemokine levels was independent of weight loss. In this RCT in individuals with diabetes type 2, with the same follow-up time as our study—26 weeks—and the same number of participants (n = 51), liraglutide treatment statistically significantly reduced MCP-1 levels [24]. Similarly to the findings of the aforementioned studies, our own investigation revealed that 26 weeks of GLP-1 RA treatment led to a statistically significant decrease in serum MCP-1 levels among patients with diabetes, dyslipidemia, and atherosclerotic peripheral artery disease. Evidently, large randomized trials are needed to unambiguously determine the effect of MCP-1 levels on the contribution to atherosclerotic plaque vulnerability and to confirm the decline of this chemokine as a potential cardioprotective mechanism.

Intercellular adhesion molecule-1 (ICAM-1) has been identified as one of the adhesion molecules implicated in the pathogenesis of atherosclerosis due to its role in facilitating the migration of leukocytes into atherosclerotic plaques [13,14]. In our investigation, individuals with confirmed atherosclerotic plaques exhibited significantly elevated serum levels of ICAM-1 in comparison to the healthy control group. Consistent with our findings, previous research suggests that heightened ICAM-1 levels correlate with increased cardiovascular risk [12]. Notably, Santos et al. did not observe a significant discrepancy in ICAM-1 levels across varying sizes of plaque in coronary arteries; however, elevated serum levels of ICAM-1 were associated with escalated cardiovascular mortality risk and were predictive of future fatal cardiovascular events [44]. In vitro GLP1-RA treatment led to inhibited ICAM-1 protein expression [45,46,47]. Similar results were obtained for experimental animal models [48]. The findings of experimental investigations were corroborated in a human clinical trial conducted by Luna-Marco et al., wherein a one-year treatment with a GLP1 receptor agonist in diabetic patients demonstrated a reduction in ICAM-1 concentration [49]. Our results are contradictory with those researchers. In our cohort, 180 days of GLP1-RA treatment led to increased ICAM-1 serum levels. The variations in the ultimate outcome could stem from differences in the duration of observation. Similar to our study, a randomized, placebo-controlled, double-blind, parallel-group clinical trial, PET/CT—LIRAFLAME, investigated the impact of 26 weeks of liraglutide treatment on serum markers associated with atherogenesis shown in the control group; an increase in ICAM-1 levels was also observed upon completion of the treatment [24]. The inconsistency observed in these findings across various studies underscores the necessity for additional Randomized Controlled Trials to definitively ascertain the impact of GLP-RA treatment on ICAM-1 levels.

The involvement of adhesion molecules of the selectin family such as E-selectin or P-selectin in the atherosclerotic process is well known, while that of L-selectin is still under investigation [8]. Experimental studies to date on the involvement of L-selectin in atherosclerosis have been contradictory [50,51]. A large multicenter study involving 2403 patients found no association between L-selectin and cardiovascular disease overall; however, in a subgroup analysis, a slight association with CVD risk was observed in Caucasian patients [52]. In our study, patients in the study group had significantly higher L-selectin concentrations than healthy volunteers; comparable results to ours were obtained by Nomura and colleagues [53]. Recent scientific reports show the association of elevated L-selectin values with microvascular complications in type 2 diabetes individuals [54]. In our cohort, we obtained a statistically significant reduction in serum L-selectin levels after 180 days of GLP-RA therapy; to the best of our knowledge, there are no results available evaluating the effect of this group of drugs on L-selectin adhesion molecule levels. Interestingly, another group of drugs with cardioprotective potential—statins—affect the reduction in these adhesion molecules, which was confirmed in this meta-analysis by Zinellu et al. in 2021 [55].

There are various limitations that apply to our research. Firstly, the size of our control group is limited—our study includes only 50 participants. Secondly, our study suffers from the absence of a control group treated for diabetes with therapies distinct from GLP-1 receptor agonists, or a placebo or an active comparator. Another limitation of our study is the lack of knowledge regarding the baseline lipid profile values of patients before the recognition of dyslipidemia, as well as the duration of this metabolic disease. These factors could result in varying initial cardiovascular risk levels among patients. Lastly, the study was conducted as a single-center trial, involving a population solely from one region of Poland and the end points may vary based on factors such as race or environmental conditions.

##  5\. Conclusions

In conclusion, our study confirmed the already-known positive effect of GLP-1RAs on metabolic and anthropometric cardiovascular risk factors. In addition, we investigated whether these drugs affect the levels of molecules responsible for the development of atherosclerosis at the stage of the adhesion of monocytes to the endothelium. We obtained a statistically significant decrease in the concentration of MCP-1 and L-selectin. This result might be accountable for the decreased cardiovascular risk observed in diabetic individuals. On the other hand, in our study group, ICAM-1 levels increased significantly after treatment; this may be attributed to the relatively short intervention duration. Additional studies, especially randomized clinical trials with long-term observation, are needed to unquestionably assess the effect of this group of drugs on the development of atherosclerotic cardiovascular disease.

## Author Contributions

Conceptualization, M.H. and M.B.; methodology, M.H. and M.B.; resources, M.H.; statistical analysis, M.K.; writing—original draft preparation, M.H. writing—review and editing, M.K. and M.B., supervision, B.O.; project administration, M.H. All authors have read and agreed to the published version of the manuscript.

## Funding

This research was funded by the Medical University of Silesia, grant number PCN-1-227/N/2/O.

## Institutional Review Board Statement

The study was conducted in accordance with the Decla-ration of Helsinki and was approved by the Bioethical Committee of the Medical University of Si-lesia 12/July/2022 PCN/CBN/0052/KB1/45/I/22.

## Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

## Data Availability Statement

Data are contained within the article.

## Acknowledgments

The authors gratefully acknowledge Grzegorz Hachuła for helping with the recruiting process, Jarosława Sprada, Kinga Banasik and Danuta Chwiędacz for laboratory maintenance, and Sabina Ryl for language support.

## Conflicts of Interest

The authors declare no conflicts of interest.

## References

  1. Mensah, G.A.; Fuster, V.; Murray, C.J.L.; Roth, G.A. Global Burden of Cardiovascular Diseases and Risks, 1990–2022. J. Am. Coll. Cardiol. **2023** , 82, 2350–2473. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Global+Burden+of+Cardiovascular+Diseases+and+Risks,+1990%E2%80%932022&author=Mensah,+G.A.&author=Fuster,+V.&author=Murray,+C.J.L.&author=Roth,+G.A.&publication_year=2023&journal=J.+Am.+Coll.+Cardiol.&volume=82&pages=2350%E2%80%932473&doi=10.1016/j.jacc.2023.11.007)] [[CrossRef](https://doi.org/10.1016/j.jacc.2023.11.007)]
  2. Frąk, W.; Wojtasińska, A.; Lisińska, W.; Młynarska, E.; Franczyk, B.; Rysz, J. Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease. Biomedicines **2022** , 10, 1938. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Pathophysiology+of+Cardiovascular+Diseases:+New+Insights+into+Molecular+Mechanisms+of+Atherosclerosis,+Arterial+Hypertension,+and+Coronary+Artery+Disease&author=Fr%C4%85k,+W.&author=Wojtasi%C5%84ska,+A.&author=Lisi%C5%84ska,+W.&author=M%C5%82ynarska,+E.&author=Franczyk,+B.&author=Rysz,+J.&publication_year=2022&journal=Biomedicines&volume=10&pages=1938&doi=10.3390/biomedicines10081938&pmid=36009488)] [[CrossRef](https://doi.org/10.3390/biomedicines10081938)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/36009488)]
  3. De Rosa, S.; Arcidiacono, B.; Chiefari, E.; Brunetti, A.; Indolfi, C.; Foti, D.P. Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links. Front. Endocrinol. **2018** , 9, 334630. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Type+2+Diabetes+Mellitus+and+Cardiovascular+Disease:+Genetic+and+Epigenetic+Links&author=De+Rosa,+S.&author=Arcidiacono,+B.&author=Chiefari,+E.&author=Brunetti,+A.&author=Indolfi,+C.&author=Foti,+D.P.&publication_year=2018&journal=Front.+Endocrinol.&volume=9&pages=334630&doi=10.3389/fendo.2018.00002&pmid=29387042)] [[CrossRef](https://doi.org/10.3389/fendo.2018.00002)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/29387042)]
  4. Maruhashi, T.; Higashi, Y. Pathophysiological Association between Diabetes Mellitus and Endothelial Dysfunction. Antioxidants **2021** , 10, 1306. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Pathophysiological+Association+between+Diabetes+Mellitus+and+Endothelial+Dysfunction&author=Maruhashi,+T.&author=Higashi,+Y.&publication_year=2021&journal=Antioxidants&volume=10&pages=1306&doi=10.3390/antiox10081306)] [[CrossRef](https://doi.org/10.3390/antiox10081306)]
  5. Matheus, A.S.; Tannus, L.R.; Cobas, R.A.; Palma, C.C.; Negrato, C.A.; Gomes, M.B. Impact of diabetes on cardiovascular disease: An update. Int. J. Hypertens. **2013** , 2013, 653789. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Impact+of+diabetes+on+cardiovascular+disease:+An+update&author=Matheus,+A.S.&author=Tannus,+L.R.&author=Cobas,+R.A.&author=Palma,+C.C.&author=Negrato,+C.A.&author=Gomes,+M.B.&publication_year=2013&journal=Int.+J.+Hypertens.&volume=2013&pages=653789&doi=10.1155/2013/653789&pmid=23533715)] [[CrossRef](https://doi.org/10.1155/2013/653789)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/23533715)]
  6. Ley, K.; Laudanna, C.; Cybulsky, M.I.; Nourshargh, S. Getting to the site of inflammation: The leukocyte adhesion cascade updated. Nat. Rev. Immunol. **2007** , 7, 678–689. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Getting+to+the+site+of+inflammation:+The+leukocyte+adhesion+cascade+updated&author=Ley,+K.&author=Laudanna,+C.&author=Cybulsky,+M.I.&author=Nourshargh,+S.&publication_year=2007&journal=Nat.+Rev.+Immunol.&volume=7&pages=678%E2%80%93689&doi=10.1038/nri2156&pmid=17717539)] [[CrossRef](https://doi.org/10.1038/nri2156)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/17717539)]
  7. Mauersberger, C.; Hinterdobler, J.; Schunkert, H.; Kessler, T.; Sager, H.B. Where the Action Is-Leukocyte Recruitment in Atherosclerosis. Front. Cardiovasc. Med. **2022** , 11, 813984. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Where+the+Action+Is-Leukocyte+Recruitment+in+Atherosclerosis&author=Mauersberger,+C.&author=Hinterdobler,+J.&author=Schunkert,+H.&author=Kessler,+T.&author=Sager,+H.B.&publication_year=2022&journal=Front.+Cardiovasc.+Med.&volume=11&pages=813984&doi=10.3389/fcvm.2021.813984)] [[CrossRef](https://doi.org/10.3389/fcvm.2021.813984)]
  8. Theofilis, P.; Sagris, M.; Oikonomou, E.; Antonopoulos, A.S.; Siasos, G.; Tsioufis, C.; Tousoulis, D. Inflammatory Mechanisms Contributing to Endothelial Dysfunction. Biomedicines **2021** , 9, 781. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Inflammatory+Mechanisms+Contributing+to+Endothelial+Dysfunction&author=Theofilis,+P.&author=Sagris,+M.&author=Oikonomou,+E.&author=Antonopoulos,+A.S.&author=Siasos,+G.&author=Tsioufis,+C.&author=Tousoulis,+D.&publication_year=2021&journal=Biomedicines&volume=9&pages=781&doi=10.3390/biomedicines9070781)] [[CrossRef](https://doi.org/10.3390/biomedicines9070781)]
  9. Tscharre, M.; Vogel, B.; Tentzeris, I.; Freynhofer, M.K.; Rohla, M.; Wojta, J.; Weiss, T.W.; Ay, C.; Huber, K.; Farhan, S. Prognostic Impact of Soluble P-Selectin on Long-Term Adverse Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention. Thromb. Haemost. **2019** , 119, 340–347. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Prognostic+Impact+of+Soluble+P-Selectin+on+Long-Term+Adverse+Cardiovascular+Outcomes+in+Patients+Undergoing+Percutaneous+Coronary+Intervention&author=Tscharre,+M.&author=Vogel,+B.&author=Tentzeris,+I.&author=Freynhofer,+M.K.&author=Rohla,+M.&author=Wojta,+J.&author=Weiss,+T.W.&author=Ay,+C.&author=Huber,+K.&author=Farhan,+S.&publication_year=2019&journal=Thromb.+Haemost.&volume=119&pages=340%E2%80%93347&doi=10.1055/s-0038-1676563)] [[CrossRef](https://doi.org/10.1055/s-0038-1676563)]
  10. Tvaroška, I.; Selvaraj, C.; Koča, J. Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review. Molecules **2020** , 25, 2835. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Selectins%E2%80%94The+Two+Dr.+Jekyll+and+Mr.+Hyde+Faces+of+Adhesion+Molecules%E2%80%94A+Review&author=Tvaro%C5%A1ka,+I.&author=Selvaraj,+C.&author=Ko%C4%8Da,+J.&publication_year=2020&journal=Molecules&volume=25&pages=2835&doi=10.3390/molecules25122835)] [[CrossRef](https://doi.org/10.3390/molecules25122835)]
  11. Muller, W.A. Getting leukocytes to the site of inflammation. Vet. Pathol. **2013** , 50, 7–22. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Getting+leukocytes+to+the+site+of+inflammation&author=Muller,+W.A.&publication_year=2013&journal=Vet.+Pathol.&volume=50&pages=7%E2%80%9322&doi=10.1177/0300985812469883&pmid=23345459)] [[CrossRef](https://doi.org/10.1177/0300985812469883)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/23345459)]
  12. Kaur, R.; Singh, V.; Kumari, P.; Singh, R.; Chopra, H.; Emran, T.B. Novel insights on the role of VCAM-1 and ICAM-1: Potential biomarkers for cardiovascular diseases. Ann. Med. Surg. **2022** , 84, 104802. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Novel+insights+on+the+role+of+VCAM-1+and+ICAM-1:+Potential+biomarkers+for+cardiovascular+diseases&author=Kaur,+R.&author=Singh,+V.&author=Kumari,+P.&author=Singh,+R.&author=Chopra,+H.&author=Emran,+T.B.&publication_year=2022&journal=Ann.+Med.+Surg.&volume=84&pages=104802&doi=10.1016/j.amsu.2022.104802&pmid=36408439)] [[CrossRef](https://doi.org/10.1016/j.amsu.2022.104802)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/36408439)]
  13. Hoke, M.; Winter, M.P.; Wagner, O.; Exner, M.; Schillinger, M.; Arnold, Z.; Mlekusch, W.; Maurer, G.; Koppensteiner, R.; Minar, E.; et al. The impact of selectins on mortality in stable carotid atherosclerosis. Thromb. Haemost. **2015** , 114, 632–638. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=The+impact+of+selectins+on+mortality+in+stable+carotid+atherosclerosis&author=Hoke,+M.&author=Winter,+M.P.&author=Wagner,+O.&author=Exner,+M.&author=Schillinger,+M.&author=Arnold,+Z.&author=Mlekusch,+W.&author=Maurer,+G.&author=Koppensteiner,+R.&author=Minar,+E.&publication_year=2015&journal=Thromb.+Haemost.&volume=114&pages=632%E2%80%93638&doi=10.1160/TH14-12-1014&pmid=25994120)] [[CrossRef](https://doi.org/10.1160/TH14-12-1014)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/25994120)]
  14. Jebari-Benslaiman, S.; Galicia-García, U.; Larrea-Sebal, A.; Olaetxea, J.R.; Alloza, I.; Vandenbroeck, K.; Benito-Vicente, A.; Martín, C. Pathophysiology of Atherosclerosis. Int. J. Mol. Sci. **2022** , 23, 3346. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Pathophysiology+of+Atherosclerosis&author=Jebari-Benslaiman,+S.&author=Galicia-Garc%C3%ADa,+U.&author=Larrea-Sebal,+A.&author=Olaetxea,+J.R.&author=Alloza,+I.&author=Vandenbroeck,+K.&author=Benito-Vicente,+A.&author=Mart%C3%ADn,+C.&publication_year=2022&journal=Int.+J.+Mol.+Sci.&volume=23&pages=3346&doi=10.3390/ijms23063346&pmid=35328769)] [[CrossRef](https://doi.org/10.3390/ijms23063346)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/35328769)]
  15. Georgakis, M.K.; Bernhagen, J.; Heitman, L.H.; Weber, C.; Dichgans, M. Targeting the CCL2-CCR2 axis for atheroprotection. Eur. Heart J. **2022** , 43, 1799–1808, Erratum in Eur. Heart J. **2022** , 43, 2424. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Targeting+the+CCL2-CCR2+axis+for+atheroprotection&author=Georgakis,+M.K.&author=Bernhagen,+J.&author=Heitman,+L.H.&author=Weber,+C.&author=Dichgans,+M.&publication_year=2022&journal=Eur.+Heart+J.&volume=43&pages=1799%E2%80%931808&doi=10.1093/eurheartj/ehac094&pmid=35567558)] [[CrossRef](https://doi.org/10.1093/eurheartj/ehac094)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/35567558)]
  16. Bernardini, F.; Nusca, A.; Coletti, F.; La Porta, Y.; Piscione, M.; Vespasiano, F.; Mangiacapra, F.; Ricottini, E.; Melfi, R.; Cavallari, I.; et al. Incretins-Based Therapies and Their Cardiovascular Effects: New Game-Changers for the Management of Patients with Diabetes and Cardiovascular Disease. Pharmaceutics **2023** , 15, 1858. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Incretins-Based+Therapies+and+Their+Cardiovascular+Effects:+New+Game-Changers+for+the+Management+of+Patients+with+Diabetes+and+Cardiovascular+Disease&author=Bernardini,+F.&author=Nusca,+A.&author=Coletti,+F.&author=La+Porta,+Y.&author=Piscione,+M.&author=Vespasiano,+F.&author=Mangiacapra,+F.&author=Ricottini,+E.&author=Melfi,+R.&author=Cavallari,+I.&publication_year=2023&journal=Pharmaceutics&volume=15&pages=1858&doi=10.3390/pharmaceutics15071858)] [[CrossRef](https://doi.org/10.3390/pharmaceutics15071858)]
  17. Hu, E.-H.; Tsai, M.-L.; Lin, Y.; Chou, T.-S.; Chen, T.-H. A Review and Meta-Analysis of the Safety and Efficacy of Using Glucagon-like Peptide-1 Receptor Agonists. Medicina **2024** , 60, 357. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=A+Review+and+Meta-Analysis+of+the+Safety+and+Efficacy+of+Using+Glucagon-like+Peptide-1+Receptor+Agonists&author=Hu,+E.-H.&author=Tsai,+M.-L.&author=Lin,+Y.&author=Chou,+T.-S.&author=Chen,+T.-H.&publication_year=2024&journal=Medicina&volume=60&pages=357&doi=10.3390/medicina60030357)] [[CrossRef](https://doi.org/10.3390/medicina60030357)]
  18. Visseren, F.L.J.; Mach, F.; Smulders, Y.M.; Carballo, D.; Koskinas, K.C.; Bäck, M.; Benetos, A.; Biffi, A.; Boavida, J.M.; Capodanno, D.; et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart J. **2021** , 42, 3227–3337, Erratum in Eur. Heart J. **2022** , 44, 4468. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=2021+ESC+Guidelines+on+cardiovascular+disease+prevention+in+clinical+practice&author=Visseren,+F.L.J.&author=Mach,+F.&author=Smulders,+Y.M.&author=Carballo,+D.&author=Koskinas,+K.C.&author=B%C3%A4ck,+M.&author=Benetos,+A.&author=Biffi,+A.&author=Boavida,+J.M.&author=Capodanno,+D.&publication_year=2021&journal=Eur.+Heart+J.&volume=42&pages=3227%E2%80%933337&doi=10.1093/eurheartj/ehab484)] [[CrossRef](https://doi.org/10.1093/eurheartj/ehab484)]
  19. American Diabetes Association. Introduction: Standards of Medical Care in Diabetes-2019. Diabetes Care **2019** , 42, S124–S138. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Introduction:+Standards+of+Medical+Care+in+Diabetes-2019&author=American+Diabetes+Association&publication_year=2019&journal=Diabetes+Care&volume=42&pages=S124%E2%80%93S138&doi=10.2337/dc19-S011)] [[CrossRef](https://doi.org/10.2337/dc19-S011)]
  20. Wong, N.D.; Sattar, N. Cardiovascular risk in diabetes mellitus: Epidemiology, assessment and prevention. Nat. Rev. Cardiol. **2023** , 20, 685–695. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Cardiovascular+risk+in+diabetes+mellitus:+Epidemiology,+assessment+and+prevention&author=Wong,+N.D.&author=Sattar,+N.&publication_year=2023&journal=Nat.+Rev.+Cardiol.&volume=20&pages=685%E2%80%93695&doi=10.1038/s41569-023-00877-z)] [[CrossRef](https://doi.org/10.1038/s41569-023-00877-z)]
  21. Nauck, M.A.; Quast, D.R.; Wefers, J.; Meier, J.J. GLP-1 receptor agonists in the treatment of type 2 diabetes—State-of-the-art. Mol. Metab. **2021** , 46, 101102. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=GLP-1+receptor+agonists+in+the+treatment+of+type+2+diabetes%E2%80%94State-of-the-art&author=Nauck,+M.A.&author=Quast,+D.R.&author=Wefers,+J.&author=Meier,+J.J.&publication_year=2021&journal=Mol.+Metab.&volume=46&pages=101102&doi=10.1016/j.molmet.2020.101102&pmid=33068776)] [[CrossRef](https://doi.org/10.1016/j.molmet.2020.101102)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/33068776)]
  22. Gupta, M.; Tummala, R.; Ghosh, R.K.; Blumenthal, C.; Philip, K.; Bandyopadhyay, D.; Ventura, H.; Deedwania, P. An update on pharmacotherapies in diabetic dyslipidemia. Prog. Cardiovasc. Dis. **2019** , 62, 334–341. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=An+update+on+pharmacotherapies+in+diabetic+dyslipidemia&author=Gupta,+M.&author=Tummala,+R.&author=Ghosh,+R.K.&author=Blumenthal,+C.&author=Philip,+K.&author=Bandyopadhyay,+D.&author=Ventura,+H.&author=Deedwania,+P.&publication_year=2019&journal=Prog.+Cardiovasc.+Dis.&volume=62&pages=334%E2%80%93341&doi=10.1016/j.pcad.2019.07.006&pmid=31442512)] [[CrossRef](https://doi.org/10.1016/j.pcad.2019.07.006)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/31442512)]
  23. Piccirillo, F.; Mastroberardino, S.; Nusca, A.; Frau, L.; Guarino, L.; Napoli, N.; Ussia, G.P.; Grigioni, F. Novel Antidiabetic Agents and Their Effects on Lipid Profile: A Single Shot for Several Cardiovascular Targets. Int. J. Mol. Sci. **2023** , 24, 10164. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Novel+Antidiabetic+Agents+and+Their+Effects+on+Lipid+Profile:+A+Single+Shot+for+Several+Cardiovascular+Targets&author=Piccirillo,+F.&author=Mastroberardino,+S.&author=Nusca,+A.&author=Frau,+L.&author=Guarino,+L.&author=Napoli,+N.&author=Ussia,+G.P.&author=Grigioni,+F.&publication_year=2023&journal=Int.+J.+Mol.+Sci.&volume=24&pages=10164&doi=10.3390/ijms241210164&pmid=37373310)] [[CrossRef](https://doi.org/10.3390/ijms241210164)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/37373310)]
  24. Ripa, R.S.; Zobel, E.H.; von Scholten, B.J.; Jensen, J.K.; Binderup, T.; Diaz, L.J.; Curovic, V.R.; Hansen, T.W.; Rossing, P.; Kjaer, A. Effect of Liraglutide on Arterial Inflammation Assessed as [18F]FDG Uptake in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. Circ. Cardiovasc. Imaging **2021** , 14, e012174. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Effect+of+Liraglutide+on+Arterial+Inflammation+Assessed+as+%5B18F%5DFDG+Uptake+in+Patients+with+Type+2+Diabetes:+A+Randomized,+Double-Blind,+Placebo-Controlled+Trial&author=Ripa,+R.S.&author=Zobel,+E.H.&author=von+Scholten,+B.J.&author=Jensen,+J.K.&author=Binderup,+T.&author=Diaz,+L.J.&author=Curovic,+V.R.&author=Hansen,+T.W.&author=Rossing,+P.&author=Kjaer,+A.&publication_year=2021&journal=Circ.+Cardiovasc.+Imaging&volume=14&pages=e012174&doi=10.1161/CIRCIMAGING.120.012174&pmid=34187185)] [[CrossRef](https://doi.org/10.1161/CIRCIMAGING.120.012174)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/34187185)]
  25. Yao, H.; Zhang, A.; Li, D.; Wu, Y.; Wang, C.; Wan, J.; Yuan, C.S. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: Systematic review and network meta-analysis. BMJ **2024** , 384, e076410. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Comparative+effectiveness+of+GLP-1+receptor+agonists+on+glycaemic+control,+body+weight,+and+lipid+profile+for+type+2+diabetes:+Systematic+review+and+network+meta-analysis&author=Yao,+H.&author=Zhang,+A.&author=Li,+D.&author=Wu,+Y.&author=Wang,+C.&author=Wan,+J.&author=Yuan,+C.S.&publication_year=2024&journal=BMJ&volume=384&pages=e076410&doi=10.1136/bmj-2023-076410&pmid=38286487)] [[CrossRef](https://doi.org/10.1136/bmj-2023-076410)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/38286487)]
  26. Popoviciu, M.S.; Păduraru, L.; Yahya, G.; Metwally, K.; Cavalu, S. Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials. Int. J. Mol. Sci. **2023** , 24, 10449. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Emerging+Role+of+GLP-1+Agonists+in+Obesity:+A+Comprehensive+Review+of+Randomised+Controlled+Trials&author=Popoviciu,+M.S.&author=P%C4%83duraru,+L.&author=Yahya,+G.&author=Metwally,+K.&author=Cavalu,+S.&publication_year=2023&journal=Int.+J.+Mol.+Sci.&volume=24&pages=10449&doi=10.3390/ijms241310449&pmid=37445623)] [[CrossRef](https://doi.org/10.3390/ijms241310449)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/37445623)]
  27. Niu, J.; Kolattukudy, P.E. Role of MCP-1 in cardiovascular disease: Molecular mechanisms and clinical implications. Clin. Sci. **2009** , 117, 95–109. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Role+of+MCP-1+in+cardiovascular+disease:+Molecular+mechanisms+and+clinical+implications&author=Niu,+J.&author=Kolattukudy,+P.E.&publication_year=2009&journal=Clin.+Sci.&volume=117&pages=95%E2%80%93109&doi=10.1042/CS20080581)] [[CrossRef](https://doi.org/10.1042/CS20080581)]
  28. Blanco-Colio, L.M.; Méndez-Barbero, N.; Pello Lázaro, A.M.; Aceña, Á.; Tarín, N.; Cristóbal, C.; Martínez-Milla, J.; González-Lorenzo, Ó.; Martín-Ventura, J.L.; Huelmos, A.; et al. MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation. J. Clin. Med. **2021** , 10, 1137. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=MCP-1+Predicts+Recurrent+Cardiovascular+Events+in+Patients+with+Persistent+Inflammation&author=Blanco-Colio,+L.M.&author=M%C3%A9ndez-Barbero,+N.&author=Pello+L%C3%A1zaro,+A.M.&author=Ace%C3%B1a,+%C3%81.&author=Tar%C3%ADn,+N.&author=Crist%C3%B3bal,+C.&author=Mart%C3%ADnez-Milla,+J.&author=Gonz%C3%A1lez-Lorenzo,+%C3%93.&author=Mart%C3%ADn-Ventura,+J.L.&author=Huelmos,+A.&publication_year=2021&journal=J.+Clin.+Med.&volume=10&pages=1137&doi=10.3390/jcm10051137)] [[CrossRef](https://doi.org/10.3390/jcm10051137)]
  29. Ylä-Herttuala, S.; Lipton, B.A.; Rosenfeld, M.E.; Särkioja, T.; Yoshimura, T.; Leonard, E.J.; Witztum, J.L.; Steinberg, D. Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. Proc. Natl. Acad. Sci. USA **1991** , 88, 5252–5256. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Expression+of+monocyte+chemoattractant+protein+1+in+macrophage-rich+areas+of+human+and+rabbit+atherosclerotic+lesions&author=Yl%C3%A4-Herttuala,+S.&author=Lipton,+B.A.&author=Rosenfeld,+M.E.&author=S%C3%A4rkioja,+T.&author=Yoshimura,+T.&author=Leonard,+E.J.&author=Witztum,+J.L.&author=Steinberg,+D.&publication_year=1991&journal=Proc.+Natl.+Acad.+Sci.+USA&volume=88&pages=5252%E2%80%935256&doi=10.1073/pnas.88.12.5252)] [[CrossRef](https://doi.org/10.1073/pnas.88.12.5252)]
  30. Ikeda, U.; Matsui, K.; Murakami, Y.; Shimada, K. Monocyte chemoattractant protein-1 and coronary artery disease. Clin. Cardiol. **2002** , 25, 143–147. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Monocyte+chemoattractant+protein-1+and+coronary+artery+disease&author=Ikeda,+U.&author=Matsui,+K.&author=Murakami,+Y.&author=Shimada,+K.&publication_year=2002&journal=Clin.+Cardiol.&volume=25&pages=143%E2%80%93147&doi=10.1002/clc.4960250403)] [[CrossRef](https://doi.org/10.1002/clc.4960250403)]
  31. Zhong, L.; Chen, W.Q.; Ji, X.P.; Zhang, M.; Zhao, Y.X.; Yao, G.H.; Zhang, P.F.; Zhang, C.; Zhang, Y. Dominant-negative mutation of monocyte chemoattractant protein-1 prevents vulnerable plaques from rupture in rabbits independent of serum lipid levels. J. Cell. Mol. Med. **2008** , 12, 2362–2371. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Dominant-negative+mutation+of+monocyte+chemoattractant+protein-1+prevents+vulnerable+plaques+from+rupture+in+rabbits+independent+of+serum+lipid+levels&author=Zhong,+L.&author=Chen,+W.Q.&author=Ji,+X.P.&author=Zhang,+M.&author=Zhao,+Y.X.&author=Yao,+G.H.&author=Zhang,+P.F.&author=Zhang,+C.&author=Zhang,+Y.&publication_year=2008&journal=J.+Cell.+Mol.+Med.&volume=12&pages=2362%E2%80%932371&doi=10.1111/j.1582-4934.2008.00261.x)] [[CrossRef](https://doi.org/10.1111/j.1582-4934.2008.00261.x)]
  32. Georgakis, M.K.; van der Laan, S.W.; Asare, Y.; Mekke, J.M.; Haitjema, S.; Schoneveld, A.H.; de Jager, S.C.A.; Nurmohamed, N.S.; Kroon, J.; Stroes, E.S.G.; et al. Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability. Arterioscler. Thromb. Vasc. Biol. **2021** , 41, 2038–2048. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Monocyte-Chemoattractant+Protein-1+Levels+in+Human+Atherosclerotic+Lesions+Associate+With+Plaque+Vulnerability&author=Georgakis,+M.K.&author=van+der+Laan,+S.W.&author=Asare,+Y.&author=Mekke,+J.M.&author=Haitjema,+S.&author=Schoneveld,+A.H.&author=de+Jager,+S.C.A.&author=Nurmohamed,+N.S.&author=Kroon,+J.&author=Stroes,+E.S.G.&publication_year=2021&journal=Arterioscler.+Thromb.+Vasc.+Biol.&volume=41&pages=2038%E2%80%932048&doi=10.1161/ATVBAHA.121.316091)] [[CrossRef](https://doi.org/10.1161/ATVBAHA.121.316091)]
  33. Georgakis, M.K.; de Lemos, J.A.; Ayers, C.; Wang, B.; Björkbacka, H.; Pana, T.A.; Thorand, B.; Sun, C.; Fani, L.; Malik, R.; et al. Association of Circulating Monocyte Chemoattractant Protein–1 Levels with Cardiovascular Mortality: A Meta-analysis of Population-Based Studies. JAMA Cardiol. **2021** , 6, 587–592. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Association+of+Circulating+Monocyte+Chemoattractant+Protein%E2%80%931+Levels+with+Cardiovascular+Mortality:+A+Meta-analysis+of+Population-Based+Studies&author=Georgakis,+M.K.&author=de+Lemos,+J.A.&author=Ayers,+C.&author=Wang,+B.&author=Bj%C3%B6rkbacka,+H.&author=Pana,+T.A.&author=Thorand,+B.&author=Sun,+C.&author=Fani,+L.&author=Malik,+R.&publication_year=2021&journal=JAMA+Cardiol.&volume=6&pages=587%E2%80%93592&doi=10.1001/jamacardio.2020.5392&pmid=33146689)] [[CrossRef](https://doi.org/10.1001/jamacardio.2020.5392)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/33146689)]
  34. Makarewicz-Wujec, M.; Henzel, J.; Kępka, C.; Kruk, M.; Wardziak, Ł.; Trochimiuk, P.; Parzonko, A.; Dzielińska, Z.; Demkow, M.; Kozłowska-Wojciechowska, M. Usefulness of MCP-1 Chemokine in the Monitoring of Patients with Coronary Artery Disease Subjected to Intensive Dietary Intervention: A Pilot Study. Nutrients **2021** , 13, 3047. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Usefulness+of+MCP-1+Chemokine+in+the+Monitoring+of+Patients+with+Coronary+Artery+Disease+Subjected+to+Intensive+Dietary+Intervention:+A+Pilot+Study&author=Makarewicz-Wujec,+M.&author=Henzel,+J.&author=K%C4%99pka,+C.&author=Kruk,+M.&author=Wardziak,+%C5%81.&author=Trochimiuk,+P.&author=Parzonko,+A.&author=Dzieli%C5%84ska,+Z.&author=Demkow,+M.&author=Koz%C5%82owska-Wojciechowska,+M.&publication_year=2021&journal=Nutrients&volume=13&pages=3047&doi=10.3390/nu13093047&pmid=34578925)] [[CrossRef](https://doi.org/10.3390/nu13093047)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/34578925)]
  35. Trøseid, M.; Lappegård, K.T.; Claudi, T.; Damås, J.K.; Mørkrid, L.; Brendberg, R.; Mollnes, T.E. Exercise reduces plasma levels of the chemokines MCP-1 and IL-8 in subjects with the metabolic syndrome. Eur. Heart J. **2004** , 25, 349–355. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Exercise+reduces+plasma+levels+of+the+chemokines+MCP-1+and+IL-8+in+subjects+with+the+metabolic+syndrome&author=Tr%C3%B8seid,+M.&author=Lappeg%C3%A5rd,+K.T.&author=Claudi,+T.&author=Dam%C3%A5s,+J.K.&author=M%C3%B8rkrid,+L.&author=Brendberg,+R.&author=Mollnes,+T.E.&publication_year=2004&journal=Eur.+Heart+J.&volume=25&pages=349%E2%80%93355&doi=10.1016/j.ehj.2003.12.006&pmid=14984925)] [[CrossRef](https://doi.org/10.1016/j.ehj.2003.12.006)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/14984925)]
  36. Romano, M.; Diomede, L.; Sironi, M.; Massimiliano, L.; Sottocorno, M.; Polentarutti, N.; Guglielmotti, A.; Albani, D.; Bruno, A.; Fruscella, P. Inhibition of monocyte chemotactic protein-1 synthesis by statins. Lab. Investig. **2000** , 80, 1095–1100. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Inhibition+of+monocyte+chemotactic+protein-1+synthesis+by+statins&author=Romano,+M.&author=Diomede,+L.&author=Sironi,+M.&author=Massimiliano,+L.&author=Sottocorno,+M.&author=Polentarutti,+N.&author=Guglielmotti,+A.&author=Albani,+D.&author=Bruno,+A.&author=Fruscella,+P.&publication_year=2000&journal=Lab.+Investig.&volume=80&pages=1095%E2%80%931100&doi=10.1038/labinvest.3780115&pmid=10908155)] [[CrossRef](https://doi.org/10.1038/labinvest.3780115)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/10908155)]
  37. Wesołowska, A.; Winiarska, H.; Owoc, J.; Borowska, M.; Domagała, J.; Mikołajczak, P.Ł.; Iskakova, S.; Dworacki, G.; Dworacka, M. Effects of Low-Dose Atorvastatin on the Peripheral Blood Mononuclear Cell Secretion of Angiogenic Factors in Type 2 Diabetes. Biomolecules **2021** , 11, 1885. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Effects+of+Low-Dose+Atorvastatin+on+the+Peripheral+Blood+Mononuclear+Cell+Secretion+of+Angiogenic+Factors+in+Type+2+Diabetes&author=Weso%C5%82owska,+A.&author=Winiarska,+H.&author=Owoc,+J.&author=Borowska,+M.&author=Domaga%C5%82a,+J.&author=Miko%C5%82ajczak,+P.%C5%81.&author=Iskakova,+S.&author=Dworacki,+G.&author=Dworacka,+M.&publication_year=2021&journal=Biomolecules&volume=11&pages=1885&doi=10.3390/biom11121885)] [[CrossRef](https://doi.org/10.3390/biom11121885)]
  38. Wang, S.; Ran, Y.; Chen, X.; Li, C.; Cheng, S.; Liu, J. Pleiotropic Effects of Simvastatin on the Regulation of Potassium Channels in Monocytes. Front. Pharmacol. **2020** , 21, 101. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Pleiotropic+Effects+of+Simvastatin+on+the+Regulation+of+Potassium+Channels+in+Monocytes&author=Wang,+S.&author=Ran,+Y.&author=Chen,+X.&author=Li,+C.&author=Cheng,+S.&author=Liu,+J.&publication_year=2020&journal=Front.+Pharmacol.&volume=21&pages=101&doi=10.3389/fphar.2020.00101)] [[CrossRef](https://doi.org/10.3389/fphar.2020.00101)]
  39. Bułdak, Ł.; Machnik, G.; Bułdak, R.J.; Łabuzek, K.; Bołdys, A.; Okopień, B. Exenatide and metformin express their anti-inflammatory effects on human monocytes/macrophages by the attenuation of MAPKs and NFκB signaling. Naunyn Schmiedeberg’s Arch. Pharmacol. **2016** , 389, 1103–1115. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Exenatide+and+metformin+express+their+anti-inflammatory+effects+on+human+monocytes/macrophages+by+the+attenuation+of+MAPKs+and+NF%CE%BAB+signaling&author=Bu%C5%82dak,+%C5%81.&author=Machnik,+G.&author=Bu%C5%82dak,+R.J.&author=%C5%81abuzek,+K.&author=Bo%C5%82dys,+A.&author=Okopie%C5%84,+B.&publication_year=2016&journal=Naunyn+Schmiedeberg%E2%80%99s+Arch.+Pharmacol.&volume=389&pages=1103%E2%80%931115&doi=10.1007/s00210-016-1277-8)] [[CrossRef](https://doi.org/10.1007/s00210-016-1277-8)]
  40. Arakawa, M.; Mita, T.; Azuma, K.; Ebato, C.; Goto, H.; Nomiyama, T.; Fujitani, Y.; Hirose, T.; Kawamori, R.; Watada, H. Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes **2010** , 59, 1030–1037. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Inhibition+of+monocyte+adhesion+to+endothelial+cells+and+attenuation+of+atherosclerotic+lesion+by+a+glucagon-like+peptide-1+receptor+agonist,+exendin-4&author=Arakawa,+M.&author=Mita,+T.&author=Azuma,+K.&author=Ebato,+C.&author=Goto,+H.&author=Nomiyama,+T.&author=Fujitani,+Y.&author=Hirose,+T.&author=Kawamori,+R.&author=Watada,+H.&publication_year=2010&journal=Diabetes&volume=59&pages=1030%E2%80%931037&doi=10.2337/db09-1694)] [[CrossRef](https://doi.org/10.2337/db09-1694)]
  41. Chaudhuri, A.; Ghanim, H.; Vora, M.; Sia, C.L.; Korzeniewski, K.; Dhindsa, S.; Makdissi, A.; Dandona, P. Exenatide exerts a potent antiinflammatory effect. J. Clin. Endocrinol. Metab. **2012** , 97, 198–207. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Exenatide+exerts+a+potent+antiinflammatory+effect&author=Chaudhuri,+A.&author=Ghanim,+H.&author=Vora,+M.&author=Sia,+C.L.&author=Korzeniewski,+K.&author=Dhindsa,+S.&author=Makdissi,+A.&author=Dandona,+P.&publication_year=2012&journal=J.+Clin.+Endocrinol.+Metab.&volume=97&pages=198%E2%80%93207&doi=10.1210/jc.2011-1508&pmid=22013105)] [[CrossRef](https://doi.org/10.1210/jc.2011-1508)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/22013105)]
  42. Liu, X.; Huang, J.; Li, J.; Mao, Q.; He, J. Effects of Liraglutide Combined with Insulin on Oxidative Stress and Serum MCP-1 and NF-kB Levels in Type 2 Diabetes. J. Coll. Physicians Surg. Pak. **2019** , 29, 218–221. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Effects+of+Liraglutide+Combined+with+Insulin+on+Oxidative+Stress+and+Serum+MCP-1+and+NF-kB+Levels+in+Type+2+Diabetes&author=Liu,+X.&author=Huang,+J.&author=Li,+J.&author=Mao,+Q.&author=He,+J.&publication_year=2019&journal=J.+Coll.+Physicians+Surg.+Pak.&volume=29&pages=218%E2%80%93221&doi=10.29271/jcpsp.2019.03.218&pmid=30823945)] [[CrossRef](https://doi.org/10.29271/jcpsp.2019.03.218)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/30823945)]
  43. Mashayekhi, M.; Beckman, J.A.; Nian, H.; Garner, E.M.; Mayfield, D.; Devin, J.K.; Koethe, J.R.; Brown, J.D.; Cahill, K.N.; Yu, C.; et al. Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial. Diabetes Obes. Metab. **2023** , 25, 570–580. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Comparative+effects+of+weight+loss+and+incretin-based+therapies+on+vascular+endothelial+function,+fibrinolysis+and+inflammation+in+individuals+with+obesity+and+prediabetes:+A+randomized+controlled+trial&author=Mashayekhi,+M.&author=Beckman,+J.A.&author=Nian,+H.&author=Garner,+E.M.&author=Mayfield,+D.&author=Devin,+J.K.&author=Koethe,+J.R.&author=Brown,+J.D.&author=Cahill,+K.N.&author=Yu,+C.&publication_year=2023&journal=Diabetes+Obes.+Metab.&volume=25&pages=570%E2%80%93580&doi=10.1111/dom.14903)] [[CrossRef](https://doi.org/10.1111/dom.14903)]
  44. Santos, J.C.D.; Cruz, M.S.; Bortolin, R.H.; Oliveira, K.M.; Araújo, J.N.G.; Duarte, V.H.R.; Silva, A.M.G.D.; Santos, I.C.C.D.; Dantas, J.M.O.; Paiva, M.S.M.O. Relationship between circulating VCAM-1, ICAM-1, E-selectin and MMP9 and the extent of coronary lesions. Clinics **2018** , 73, e203. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Relationship+between+circulating+VCAM-1,+ICAM-1,+E-selectin+and+MMP9+and+the+extent+of+coronary+lesions&author=Santos,+J.C.D.&author=Cruz,+M.S.&author=Bortolin,+R.H.&author=Oliveira,+K.M.&author=Ara%C3%BAjo,+J.N.G.&author=Duarte,+V.H.R.&author=Silva,+A.M.G.D.&author=Santos,+I.C.C.D.&author=Dantas,+J.M.O.&author=Paiva,+M.S.M.O.&publication_year=2018&journal=Clinics&volume=73&pages=e203&doi=10.6061/clinics/2018/e203&pmid=29846413)] [[CrossRef](https://doi.org/10.6061/clinics/2018/e203)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/29846413)]
  45. Guo, L.; Qiao, Y.; Zhang, L.; Pan, Q. Protective Role of Glucagon-Like Peptide-1 against High-Glucose-Induced Endothelial Oxidative Damage. Medicine **2015** , 94, e2055. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Protective+Role+of+Glucagon-Like+Peptide-1+against+High-Glucose-Induced+Endothelial+Oxidative+Damage&author=Guo,+L.&author=Qiao,+Y.&author=Zhang,+L.&author=Pan,+Q.&publication_year=2015&journal=Medicine&volume=94&pages=e2055&doi=10.1097/MD.0000000000002055)] [[CrossRef](https://doi.org/10.1097/MD.0000000000002055)]
  46. Dorecka, M.; Siemianowicz, K.; Francuz, T.; Garczorz, W.; Chyra, A.; Klych, A.; Romaniuk, W. Exendin-4 and GLP-1 decreases induced expression of ICAM-1, VCAM-1 and RAGE in human retinal pigment epithelial cells. Pharmacol. Rep. **2013** , 65, 884–890. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Exendin-4+and+GLP-1+decreases+induced+expression+of+ICAM-1,+VCAM-1+and+RAGE+in+human+retinal+pigment+epithelial+cells&author=Dorecka,+M.&author=Siemianowicz,+K.&author=Francuz,+T.&author=Garczorz,+W.&author=Chyra,+A.&author=Klych,+A.&author=Romaniuk,+W.&publication_year=2013&journal=Pharmacol.+Rep.&volume=65&pages=884%E2%80%93890&doi=10.1016/S1734-1140\(13\)71069-7&pmid=24145082)] [[CrossRef](https://doi.org/10.1016/S1734-1140\(13\)71069-7)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/24145082)]
  47. Liu, H.; Dear, A.E.; Knudsen, L.B.; Simpson, R.W. A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules. J. Endocrinol. **2009** , 201, 59–66, Epub 2009 Jan 9. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=A+long-acting+glucagon-like+peptide-1+analogue+attenuates+induction+of+plasminogen+activator+inhibitor+type-1+and+vascular+adhesion+molecules&author=Liu,+H.&author=Dear,+A.E.&author=Knudsen,+L.B.&author=Simpson,+R.W.&publication_year=2009&journal=J.+Endocrinol.&volume=201&pages=59%E2%80%9366&doi=10.1677/JOE-08-0468&pmid=19136619)] [[CrossRef](https://doi.org/10.1677/JOE-08-0468)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/19136619)]
  48. Gaspari, T.; Liu, H.; Welungoda, I.; Hu, Y.; Widdop, R.E.; Knudsen, L.B.; Simpson, R.W.; Dear, A.E. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model. Diabetes Vasc. Dis. Res. **2011** , 8, 117–124. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=A+GLP-1+receptor+agonist+liraglutide+inhibits+endothelial+cell+dysfunction+and+vascular+adhesion+molecule+expression+in+an+ApoE-/-+mouse+model&author=Gaspari,+T.&author=Liu,+H.&author=Welungoda,+I.&author=Hu,+Y.&author=Widdop,+R.E.&author=Knudsen,+L.B.&author=Simpson,+R.W.&author=Dear,+A.E.&publication_year=2011&journal=Diabetes+Vasc.+Dis.+Res.&volume=8&pages=117%E2%80%93124&doi=10.1177/1479164111404257)] [[CrossRef](https://doi.org/10.1177/1479164111404257)]
  49. Luna-Marco, C.; de Marañon, A.M.; Hermo-Argibay, A.; Rodriguez-Hernandez, Y.; Hermenejildo, J.; Fernandez-Reyes, M.; Apostolova, N.; Vila, J.; Sola, E.; Morillas, C.; et al. Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes. Redox Biol. **2023** , 66, 102849. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Effects+of+GLP-1+receptor+agonists+on+mitochondrial+function,+inflammatory+markers+and+leukocyte-endothelium+interactions+in+type+2+diabetes&author=Luna-Marco,+C.&author=de+Mara%C3%B1on,+A.M.&author=Hermo-Argibay,+A.&author=Rodriguez-Hernandez,+Y.&author=Hermenejildo,+J.&author=Fernandez-Reyes,+M.&author=Apostolova,+N.&author=Vila,+J.&author=Sola,+E.&author=Morillas,+C.&publication_year=2023&journal=Redox+Biol.&volume=66&pages=102849&doi=10.1016/j.redox.2023.102849)] [[CrossRef](https://doi.org/10.1016/j.redox.2023.102849)]
  50. Galkina, E.; Kadl, A.; Sanders, J.; Varughese, D.; Sarembock, I.J.; Ley, K. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J. Exp. Med. **2006** , 203, 1273–1282. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Lymphocyte+recruitment+into+the+aortic+wall+before+and+during+development+of+atherosclerosis+is+partially+L-selectin+dependent&author=Galkina,+E.&author=Kadl,+A.&author=Sanders,+J.&author=Varughese,+D.&author=Sarembock,+I.J.&author=Ley,+K.&publication_year=2006&journal=J.+Exp.+Med.&volume=203&pages=1273%E2%80%931282&doi=10.1084/jem.20052205)] [[CrossRef](https://doi.org/10.1084/jem.20052205)]
  51. Rozenberg, I.; Sluka, S.H.; Mocharla, P.; Hallenberg, A.; Rotzius, P.; Borén, J.; Kränkel, N.; Landmesser, U.; Borsig, L.; Lüscher, T.F.; et al. Deletion of L-selectin increases atherosclerosis development in ApoE-/- mice. PLoS ONE **2011** , 6, e21675. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Deletion+of+L-selectin+increases+atherosclerosis+development+in+ApoE-/-+mice&author=Rozenberg,+I.&author=Sluka,+S.H.&author=Mocharla,+P.&author=Hallenberg,+A.&author=Rotzius,+P.&author=Bor%C3%A9n,+J.&author=Kr%C3%A4nkel,+N.&author=Landmesser,+U.&author=Borsig,+L.&author=L%C3%BCscher,+T.F.&publication_year=2011&journal=PLoS+ONE&volume=6&pages=e21675&doi=10.1371/journal.pone.0021675)] [[CrossRef](https://doi.org/10.1371/journal.pone.0021675)]
  52. Berardi, C.; Decker, P.A.; Kirsch, P.S.; de Andrade, M.; Tsai, M.Y.; Pankow, J.S.; Sale, M.M.; Sicotte, H.; Tang, W.; Hanson, N.; et al. Plasma and serum L-selectin and clinical and subclinical cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA). Transl. Res. **2014** , 163, 585–592. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Plasma+and+serum+L-selectin+and+clinical+and+subclinical+cardiovascular+disease:+The+Multi-Ethnic+Study+of+Atherosclerosis+\(MESA\)&author=Berardi,+C.&author=Decker,+P.A.&author=Kirsch,+P.S.&author=de+Andrade,+M.&author=Tsai,+M.Y.&author=Pankow,+J.S.&author=Sale,+M.M.&author=Sicotte,+H.&author=Tang,+W.&author=Hanson,+N.&publication_year=2014&journal=Transl.+Res.&volume=163&pages=585%E2%80%93592&doi=10.1016/j.trsl.2014.02.001&pmid=24631064)] [[CrossRef](https://doi.org/10.1016/j.trsl.2014.02.001)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/24631064)]
  53. Nomura, S.; Shouzu, A.; Omoto, S.; Inami, N.; Tanaka, A.; Nanba, M.; Shouda, Y.; Takahashi, N.; Kimura, Y.; Iwasaka, T. Correlation between adiponectin and reduction of cell adhesion molecules after pitavastatin treatment in hyperlipidemic patients with type 2 diabetes mellitus. Thromb. Res. **2008** , 122, 39–45. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Correlation+between+adiponectin+and+reduction+of+cell+adhesion+molecules+after+pitavastatin+treatment+in+hyperlipidemic+patients+with+type+2+diabetes+mellitus&author=Nomura,+S.&author=Shouzu,+A.&author=Omoto,+S.&author=Inami,+N.&author=Tanaka,+A.&author=Nanba,+M.&author=Shouda,+Y.&author=Takahashi,+N.&author=Kimura,+Y.&author=Iwasaka,+T.&publication_year=2008&journal=Thromb.+Res.&volume=122&pages=39%E2%80%9345&doi=10.1016/j.thromres.2007.08.013&pmid=17920663)] [[CrossRef](https://doi.org/10.1016/j.thromres.2007.08.013)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/17920663)]
  54. Siddiqui, K.; George, T.P.; Mujammami, M.; Isnani, A.; Alfadda, A.A. The association of cell adhesion molecules and selectins (VCAM-1, ICAM-1, E-selectin, L-selectin, and P-selectin) with microvascular complications in patients with type 2 diabetes: A follow-up study. Front. Endocrinol. **2023** , 14, 1072288. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=The+association+of+cell+adhesion+molecules+and+selectins+\(VCAM-1,+ICAM-1,+E-selectin,+L-selectin,+and+P-selectin\)+with+microvascular+complications+in+patients+with+type+2+diabetes:+A+follow-up+study&author=Siddiqui,+K.&author=George,+T.P.&author=Mujammami,+M.&author=Isnani,+A.&author=Alfadda,+A.A.&publication_year=2023&journal=Front.+Endocrinol.&volume=14&pages=1072288&doi=10.3389/fendo.2023.1072288)] [[CrossRef](https://doi.org/10.3389/fendo.2023.1072288)]
  55. Zinellu, A.; Mangoni, A.A. Systematic Review and Meta-Analysis of the Effect of Statins on Circulating E-Selectin, L-Selectin, and P-Selectin. Biomedicines **2021** , 9, 1707. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Systematic+Review+and+Meta-Analysis+of+the+Effect+of+Statins+on+Circulating+E-Selectin,+L-Selectin,+and+P-Selectin&author=Zinellu,+A.&author=Mangoni,+A.A.&publication_year=2021&journal=Biomedicines&volume=9&pages=1707&doi=10.3390/biomedicines9111707&pmid=34829936)] [[CrossRef](https://doi.org/10.3390/biomedicines9111707)] [[PubMed](https://www.ncbi.nlm.nih.gov/pubmed/34829936)]



**Figure 1.** Concentration of ICAM-1 in study group before and after intervention. 

**Figure 1.** Concentration of ICAM-1 in study group before and after intervention.

**Figure 2.** Concentration of L-selectin in study group before and after intervention. 

**Figure 2.** Concentration of L-selectin in study group before and after intervention.

**Figure 3.** Concentration of MCP-1 in study group before and after intervention. 

**Figure 3.** Concentration of MCP-1 in study group before and after intervention.

**Table 1.** Complete treatment data for the study group. ACEI—angiotensin converting enzyme inhibitor; ARB—angiotensin receptor blocker; DPP-4—dipeptidyl peptidase-4; SGLT2—sodium–glucosium-like transporter 2; n—number of participants; %—a percentage of the survey group. 

**Table 1.** Complete treatment data for the study group. ACEI—angiotensin converting enzyme inhibitor; ARB—angiotensin receptor blocker; DPP-4—dipeptidyl peptidase-4; SGLT2—sodium–glucosium-like transporter 2; n—number of participants; %—a percentage of the survey group.

**Diabetes Treatment, n (%)**|   
---|---  
Metformin| 49 (98%)  
Sulfonylurea| 22 (44%)  
Insulin| 14 (28%)  
SGLT2 inhibitors| 10 (20%)  
DPP-4 inhibitors| 4 (8%)  
**Other treatment, n (%)**|   
HMG-CoA reductase inhibitor| 42 (84%)  
ACEI/ARB| 36 (72%)  
Bblokers | 21 (42%)  
Indapamide| 12 (24%)  
Fibrates| 10 (20%)  
Thiazide diuretics| 10 (20%)  
Acetylsalicylic acid| 10 (20%)  
Loop diuretics| 8 (16%)  
  
**Table 2.** Baseline characteristics of patients. BMI—body mass index; SBP—systolic blood pressure; WHO—World Health Organization. 

**Table 2.** Baseline characteristics of patients. BMI—body mass index; SBP—systolic blood pressure; WHO—World Health Organization.

| Study Group | Control Group  
---|---|---  
Number of patients, n| 50| 26  
Age, years| 60.8 | 33.1   
Women, n (%)| 27 (54%)| 13 (50%)  
Men, n (%)| 23 (46%)| 13 (50%)  
Body mass, kg | 99.9| 69.7  
Height, cm| 168.7| 175.3  
BMI, kg/m2| 35| 22.5  
Overweight n(%)| 12 (24%)| 5 (19%)  
Obese, n (%)| 35 (70%)| 0  
SBP, mmHg| 135| 122  
WHO guidelines on physical activity, n (%)| 20 (40%)| 14 (54%)  
Smokers, n (%)|  |   
Active| 9 (18%)| 1 (4%)  
Past| 11 (22%)| 12 (46%)  
Alcohol abuse, %| 0| 0  
Co-morbidity, n (%)|  |   
Hypertension| 40 (80%)| 0  
Chronic kidney diseases| 9 (18%)| 0  
Thyroid diseases| 8 (16%)| 0  
Heart failure| 4 (8%)| 0  
  
**Table 3.** Comparison of biochemical effects between the control and study groups before and after intervention. ALT—alanine transaminase; AST—aspartate transaminase; BMI—body mass index; FIB-4—fibrosis-4 score; GFR—glomerular filtration rate; GGTP—gamma-glutamyl transpeptidase; HbA1C—glycated hemoglobin; HDL—high-density lipoprotein cholesterol; LDL—low-density lipoprotein cholesterol; non-HDL—non-high-density lipoprotein cholesterol; TG—triglycerides; TC—total cholesterol; statistic significance: *—comparison between study group before and after treatment p < 0.001; **—comparison between study group before and after treatment p < 0.05; #—comparison between control and study group before treatment p < 0.001. 

**Table 3.** Comparison of biochemical effects between the control and study groups before and after intervention. ALT—alanine transaminase; AST—aspartate transaminase; BMI—body mass index; FIB-4—fibrosis-4 score; GFR—glomerular filtration rate; GGTP—gamma-glutamyl transpeptidase; HbA1C—glycated hemoglobin; HDL—high-density lipoprotein cholesterol; LDL—low-density lipoprotein cholesterol; non-HDL—non-high-density lipoprotein cholesterol; TG—triglycerides; TC—total cholesterol; statistic significance: *—comparison between study group before and after treatment p < 0.001; **—comparison between study group before and after treatment p < 0.05; #—comparison between control and study group before treatment p < 0.001.

|  Control Group |  Study Group before Treatment |  Study Group after Treatment   
---|---|---|---  
Mean |  Mean |  Mean   
BMI kg/m2|  22.46 #|  35.02 *,#|  33.21 *   
HbA1C % |  5.5 #|  8.68 *,#|  7.56 *   
GFR mL/min/1.73 m2|  96.5 #|  69.76 #|  73.1   
|  Median |  Median |  Median   
Glucose mg/dL |  89 #|  160.5 *,#|  138.3 *   
TC mg/dL |  173.8 |  166.55 |  169.1   
LDL mg/dL |  90.5 |  83 |  80.5   
HDL mg/dL |  64.3 #|  48.95 #|  50.65   
non-HDL mg/dL |  109 |  113.7 |  107.8   
TG mg/dL |  86.5 #|  167.95 #|  146.5   
Creatinine mg/dL |  0.93 #|  1.06 #|  1.04   
ALT U/I |  17 #|  25.5 #|  29   
AST U/I |  18.5 #|  28 #|  25   
De Ritis ratio (ALT/ASP) |  1.11 |  0.98 ** |  0.85 **   
GGTP U/I |  18 #|  37 #|  35   
FIB-4 |  0.66 #|  1.5 #|  1.3 *   
  
**Table 4.** Correlation between changes in weight, body mass index and concentration of glycated hemoglobin and concentrations of investigated molecules. HbA1C—glycated hemoglobin; ICAM-1—intercellular adhesion molecule-1; MCP-1—monocyte chemoattractant protein-1; BMI—body mass index. 

**Table 4.** Correlation between changes in weight, body mass index and concentration of glycated hemoglobin and concentrations of investigated molecules. HbA1C—glycated hemoglobin; ICAM-1—intercellular adhesion molecule-1; MCP-1—monocyte chemoattractant protein-1; BMI—body mass index.

| ΔHbA1C| ΔWeight| ΔBMI  
---|---|---|---  
ΔICAM-1| ρ = −0.31, p < 0.05| ρ = −0.24, p > 0.05| ρ = 0.20, p > 0.05  
ΔL-selectine| ρ = 0.13, p > 0.05| ρ = 0.13, p > 0.05| ρ = 0.15, p > 0.05  
ΔMCP-1| ρ = 0.15, p > 0.05| ρ = −0.014, p > 0.05| ρ = 0.01, p > 0.05  
  
**Table 5.** Correlation between changes in lipid profile and investigated molecules. TCh—total cholesterol; LDL—low-density lipoprotein; HDL—high-density lipoprotein; TG—triglycerides ICAM-1—intercellular adhesion molecule-1; MCP-1—monocyte chemoattractant protein-1. 

**Table 5.** Correlation between changes in lipid profile and investigated molecules. TCh—total cholesterol; LDL—low-density lipoprotein; HDL—high-density lipoprotein; TG—triglycerides ICAM-1—intercellular adhesion molecule-1; MCP-1—monocyte chemoattractant protein-1.

| ΔTCh| ΔLDL| Δnon-HDL| ΔHDL| ΔTG  
---|---|---|---|---|---  
ΔICAM-1| ρ = −0.11, p > 0.05| ρ = −0.06, p > 0.05| ρ = −0.06, p > 0.05| ρ = −0.001, p > 0.05| ρ = −0.16, p > 0.05  
ΔL-selectine| ρ = −0.004, p > 0.05| ρ = −0.21, p > 0.05| ρ = 0.004, p > 0.05| ρ = −0.27, p > 0.05| ρ = −0.002, p > 0.05  
ΔMCP-1| ρ = 0.15, p > 0.05| ρ = 0.11, p > 0.05| ρ = 0.16, p > 0.05| ρ = −0.034, p > 0.05| ρ = 0.26, p > 0.05  
  
| **Disclaimer/Publisher’s Note:** The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.  
---|---  
  
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<https://creativecommons.org/licenses/by/4.0/>).

## Share and Cite


**MDPI and ACS Style**

Hachuła, M.; Basiak, M.; Kosowski, M.; Okopień, B. Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis. _Life_ **2024** , _14_ , 690. https://doi.org/10.3390/life14060690 

**AMA Style**  


Hachuła M, Basiak M, Kosowski M, Okopień B. Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis. _Life_. 2024; 14(6):690. https://doi.org/10.3390/life14060690 

**Chicago/Turabian Style**  


Hachuła, Marcin, Marcin Basiak, Michał Kosowski, and Bogusław Okopień. 2024\. "Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis" _Life_ 14, no. 6: 690. https://doi.org/10.3390/life14060690 

**APA Style**  


Hachuła, M., Basiak, M., Kosowski, M., & Okopień, B. (2024). Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis. _Life_ , _14_(6), 690. https://doi.org/10.3390/life14060690 

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details [here](https://www.mdpi.com/about/announcements/784). 

## Article Metrics

No

No

### Article Access Statistics

For more information on the journal statistics, click [here](/journal/life/stats). 

Multiple requests from the same IP address are counted as one view. 

Zoom | Orient  | As Lines  | As Sticks  | As Cartoon  | As Surface  | Previous Scene | Next Scene

## Cite

Export citation file: [BibTeX](javascript:window.document.forms\['export-bibtex'\].submit\(\)) | [EndNote](javascript:window.document.forms\['export-endnote'\].submit\(\)) | [RIS](javascript:window.document.forms\['export-ris'\].submit\(\))

**MDPI and ACS Style**

Hachuła, M.; Basiak, M.; Kosowski, M.; Okopień, B. Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis. _Life_ **2024** , _14_ , 690. https://doi.org/10.3390/life14060690 

**AMA Style**  


Hachuła M, Basiak M, Kosowski M, Okopień B. Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis. _Life_. 2024; 14(6):690. https://doi.org/10.3390/life14060690 

**Chicago/Turabian Style**  


Hachuła, Marcin, Marcin Basiak, Michał Kosowski, and Bogusław Okopień. 2024\. "Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis" _Life_ 14, no. 6: 690. https://doi.org/10.3390/life14060690 

**APA Style**  


Hachuła, M., Basiak, M., Kosowski, M., & Okopień, B. (2024). Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis. _Life_ , _14_(6), 690. https://doi.org/10.3390/life14060690 

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details [here](https://www.mdpi.com/about/announcements/784). 

_clear_

_[Life](/journal/life)_ , EISSN 2075-1729, Published by MDPI 

[RSS](/rss/journal/life) [Content Alert](/journal/life/toc-alert)

###  Further Information 

[ Article Processing Charges ](/apc) [ Pay an Invoice ](/about/payment) [ Open Access Policy ](/openaccess) [ Contact MDPI ](/about/contact) [ Jobs at MDPI ](https://careers.mdpi.com)

###  Guidelines 

[ For Authors ](/authors) [ For Reviewers ](/reviewers) [ For Editors ](/editors) [ For Librarians ](/librarians) [ For Publishers ](/publishing_services) [ For Societies ](/societies) [ For Conference Organizers ](/conference_organizers)

###  MDPI Initiatives 

[ Sciforum ](https://sciforum.net) [ MDPI Books ](https://www.mdpi.com/books) [ Preprints.org ](https://www.preprints.org) [ Scilit ](https://www.scilit.com) [ SciProfiles ](https://sciprofiles.com?utm_source=mpdi.com&utm_medium=bottom_menu&utm_campaign=initiative) [ Encyclopedia ](https://encyclopedia.pub) [ JAMS ](https://jams.pub) [ Proceedings Series ](/about/proceedings)

###  Follow MDPI 

[ LinkedIn ](https://www.linkedin.com/company/mdpi) [ Facebook ](https://www.facebook.com/MDPIOpenAccessPublishing) [ Twitter ](https://twitter.com/MDPIOpenAccess)

![MDPI](https://pub.mdpi-res.com/img/design/mdpi-pub-logo-white-small.png?71d18e5f805839ab?1740558760)

Subscribe to receive issue release notifications and newsletters from MDPI journals 

Acoustics Acta Microbiologica Hellenica Actuators Adhesives Administrative Sciences Adolescents Advances in Respiratory Medicine Aerobiology Aerospace Agriculture AgriEngineering Agrochemicals Agronomy AI AI Sensors Air Algorithms Allergies Alloys Analytica Analytics Anatomia Anesthesia Research Animals Antibiotics Antibodies Antioxidants Applied Biosciences Applied Mechanics Applied Microbiology Applied Nano Applied Sciences Applied System Innovation AppliedChem AppliedMath Aquaculture Journal Architecture Arthropoda Arts Astronomy Atmosphere Atoms Audiology Research Automation Axioms Bacteria Batteries Behavioral Sciences Beverages Big Data and Cognitive Computing BioChem Bioengineering Biologics Biology Biology and Life Sciences Forum Biomass Biomechanics BioMed Biomedicines BioMedInformatics Biomimetics Biomolecules Biophysica Biosensors Biosphere BioTech Birds Blockchains Brain Sciences Buildings Businesses C Cancers Cardiogenetics Catalysts Cells Ceramics Challenges ChemEngineering Chemistry Chemistry Proceedings Chemosensors Children Chips CivilEng Clean Technologies Climate Clinical and Translational Neuroscience Clinical Bioenergetics Clinics and Practice Clocks & Sleep Coasts Coatings Colloids and Interfaces Colorants Commodities Complexities Complications Compounds Computation Computer Sciences & Mathematics Forum Computers Condensed Matter Conservation Construction Materials Corrosion and Materials Degradation Cosmetics COVID Craniomaxillofacial Trauma & Reconstruction Crops Cryo Cryptography Crystals Current Issues in Molecular Biology Current Oncology Dairy Data Dentistry Journal Dermato Dermatopathology Designs Diabetology Diagnostics Dietetics Digital Disabilities Diseases Diversity DNA Drones Drugs and Drug Candidates Dynamics Earth Ecologies Econometrics Economies Education Sciences Electricity Electrochem Electronic Materials Electronics Emergency Care and Medicine Encyclopedia Endocrines Energies Energy Storage and Applications Eng Engineering Proceedings Entropy Environmental and Earth Sciences Proceedings Environments Epidemiologia Epigenomes European Burn Journal European Journal of Investigation in Health, Psychology and Education Fermentation Fibers FinTech Fire Fishes Fluids Foods Forecasting Forensic Sciences Forests Fossil Studies Foundations Fractal and Fractional Fuels Future Future Internet Future Pharmacology Future Transportation Galaxies Games Gases Gastroenterology Insights Gastrointestinal Disorders Gastronomy Gels Genealogy Genes Geographies GeoHazards Geomatics Geometry Geosciences Geotechnics Geriatrics Glacies Gout, Urate, and Crystal Deposition Disease Grasses Green Health Hardware Healthcare Hearts Hemato Hematology Reports Heritage Histories Horticulturae Hospitals Humanities Humans Hydrobiology Hydrogen Hydrology Hygiene Immuno Infectious Disease Reports Informatics Information Infrastructures Inorganics Insects Instruments Intelligent Infrastructure and Construction International Journal of Environmental Research and Public Health International Journal of Financial Studies International Journal of Molecular Sciences International Journal of Neonatal Screening International Journal of Orofacial Myology and Myofunctional Therapy International Journal of Plant Biology International Journal of Topology International Journal of Translational Medicine International Journal of Turbomachinery, Propulsion and Power International Medical Education Inventions IoT ISPRS International Journal of Geo-Information J Journal of Ageing and Longevity Journal of Cardiovascular Development and Disease Journal of Clinical & Translational Ophthalmology Journal of Clinical Medicine Journal of Composites Science Journal of Cybersecurity and Privacy Journal of Dementia and Alzheimer's Disease Journal of Developmental Biology Journal of Experimental and Theoretical Analyses Journal of Eye Movement Research Journal of Functional Biomaterials Journal of Functional Morphology and Kinesiology Journal of Fungi Journal of Imaging Journal of Intelligence Journal of Low Power Electronics and Applications Journal of Manufacturing and Materials Processing Journal of Marine Science and Engineering Journal of Market Access & Health Policy Journal of Mind and Medical Sciences Journal of Molecular Pathology Journal of Nanotheranostics Journal of Nuclear Engineering Journal of Otorhinolaryngology, Hearing and Balance Medicine Journal of Parks Journal of Personalized Medicine Journal of Pharmaceutical and BioTech Industry Journal of Respiration Journal of Risk and Financial Management Journal of Sensor and Actuator Networks Journal of the Oman Medical Association Journal of Theoretical and Applied Electronic Commerce Research Journal of Vascular Diseases Journal of Xenobiotics Journal of Zoological and Botanical Gardens Journalism and Media Kidney and Dialysis Kinases and Phosphatases Knowledge LabMed Laboratories Land Languages Laws Life Limnological Review Lipidology Liquids Literature Livers Logics Logistics Lubricants Lymphatics Machine Learning and Knowledge Extraction Machines Macromol Magnetism Magnetochemistry Marine Drugs Materials Materials Proceedings Mathematical and Computational Applications Mathematics Medical Sciences Medical Sciences Forum Medicina Medicines Membranes Merits Metabolites Metals Meteorology Methane Methods and Protocols Metrics Metrology Micro Microbiology Research Micromachines Microorganisms Microplastics Microwave Minerals Mining Modelling Modern Mathematical Physics Molbank Molecules Multimedia Multimodal Technologies and Interaction Muscles Nanoenergy Advances Nanomanufacturing Nanomaterials NDT Network Neuroglia Neurology International NeuroSci Nitrogen Non-Coding RNA Nursing Reports Nutraceuticals Nutrients Obesities Oceans Onco Optics Oral Organics Organoids Osteology Oxygen Parasitologia Particles Pathogens Pathophysiology Pediatric Reports Pets Pharmaceuticals Pharmaceutics Pharmacoepidemiology Pharmacy Philosophies Photochem Photonics Phycology Physchem Physical Sciences Forum Physics Physiologia Plants Plasma Platforms Pollutants Polymers Polysaccharides Populations Poultry Powders Proceedings Processes Prosthesis Proteomes Psychiatry International Psychoactives Psychology International Publications Purification Quantum Beam Science Quantum Reports Quaternary Radiation Reactions Real Estate Receptors Recycling Regional Science and Environmental Economics Religions Remote Sensing Reports Reproductive Medicine Resources Rheumato Risks Robotics Ruminants Safety Sci Scientia Pharmaceutica Sclerosis Seeds Sensors Separations Sexes Signals Sinusitis Smart Cities Social Sciences Société Internationale d’Urologie Journal Societies Software Soil Systems Solar Solids Spectroscopy Journal Sports Standards Stats Stresses Surfaces Surgeries Surgical Techniques Development Sustainability Sustainable Chemistry Symmetry SynBio Systems Targets Taxonomy Technologies Telecom Textiles Thalassemia Reports Therapeutics Thermo Time and Space Tomography Tourism and Hospitality Toxics Toxins Transplantology Trauma Care Trends in Higher Education Tropical Medicine and Infectious Disease Universe Urban Science Uro Vaccines Vehicles Venereology Veterinary Sciences Vibration Virtual Worlds Viruses Vision Waste Water Wild Wind Women World World Electric Vehicle Journal Youth Zoonotic Diseases Subscribe

© 1996-2025 MDPI (Basel, Switzerland) unless otherwise stated 

Disclaimer 

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. 

[ Terms and Conditions ](/about/terms-and-conditions) [ Privacy Policy ](/about/privacy)

We use cookies on our website to ensure you get the best experience.  
Read more about our cookies [here](/about/privacy). 

[Accept](/accept_cookies)

## Share Link


Copy

_clear_

## Share

https://www.mdpi.com/2806912

_clear_

Back to TopTop


