# documents

url: https://www.benthamdirect.com/content/journals/cpd/10.2174/1381612829666230703161058
scrape_date: 2025-02-28T16:00:06.298121
content_type: markdown
hash: 7144d8e242bd89d05f1d00b2459272e7b5ff6aee1a4d3b8caf71e1255928c9da
title:
Novel Approaches to the Management of Diabetes Mellitus in Patients with Coronary Artery Disease | Bentham Science Publishers

content:
Skip to content 

2000

[![Bentham Science Publishers](/images/hybrid/logo/logo.svg)](/)

  * ![search icon](/images/hybrid/icon/search.svg)

![search icon](/images/hybrid/icon/search.svg) [ ADVANCED SEARCH ](/search/advancedsearch)

  * [ ![account icon](/images/hybrid/icon/account_circle.svg) ](/registration/signin-or-register.action?signInTarget=%2Fcontent%2Fjournals%2Fcpd%2F10.2174%2F1381612829666230703161058 "Login or Register")
  * [ ![shopping cart icon](/images/hybrid/icon/shopping_cart.svg) ](/cart "Shopping cart")
  *     * [Journals](/content/journals "Journals")
    * [Books](/content/books "Books")
    * [Subjects](/content/subjects "Subjects")
    * [Collections](https://www.eurekaselect.com/alldiseases "Collections")
    * [For Authors and Editors](/info-for-authors "For Authors and Editors")
    * For Librarians
      * [Librarian FAQs](/librarians-faq "Librarian FAQs")
      * [Librarian Resources](/info-for-librarians "Librarian Resources")
    * Help
      * [SA ePublications User Guide](/upload/marketing/SAePublications_User_Guide_Online_compressed.pdf "SA ePublications User Guide")
      * [How to subscribe](/how-to-subscribe "How to subscribe")
      * [FAQs](/faq "FAQs")




  * Publications __
    * [Journals](/content/journals "Journals")
    * [Books](/content/books "Books")
    * [Subjects](/content/subjects "Subjects")
    * [Collections](https://www.eurekaselect.com/alldiseases "Collections")
  * Resources __
    * [How to get access / subscribe](https://www.eurekaselect.com/order-subscription "How to get access / subscribe")
    * [Information for authors and editors](/info-for-authors "Information for authors and editors")
    * [Information for librarians](/info-for-librarians "Information for librarians")
    * [Open Access policy](/oa-policy "Open Access policy")
    * [User Guide](/user-guide  "User Guide")
  * About __
    * [About Bentham](/about-us "About Bentham")
    * [Mission Statement & History](/Mission Statement & History "Mission Statement & History")
    * [FAQ](/faq  "FAQ")
  * [ Contact Us ](/Contact Us "Contact Us")



Toggle navigation Tools __ Toggle navigation Share __

### __Share

### __Tools

  * __Add to my favourites

  * Create Publication Alert 

Create Citation Alert 

Create Correction Alert 

  * __Export citation
    * [BibTEX](/content/journals/cpd/10.2174/1381612829666230703161058/cite/bibtex "Link to export in BibTEX format")
    * [Endnote](/content/journals/cpd/10.2174/1381612829666230703161058/cite/endnote "Link to export in Endnote format")
    * [Zotero](/content/journals/cpd/10.2174/1381612829666230703161058/cite/bibtex "Link to export in Zotero format")
    * [Medlars](/content/journals/cpd/10.2174/1381612829666230703161058/cite/medline "Link to export in MEDLARS text")
    * [RefWorks](/content/journals/cpd/10.2174/1381612829666230703161058/cite/refworks "Link to export in RefWorks format")
    * [Mendeley](http://www.mendeley.com/import/?url=https%3A%2F%2Fwww.benthamdirect.com%2Fcontent%2Fjournals%2Fcpd%2F10.2174%2F1381612829666230703161058 "Link to export to Mendeley")
  * [__Recommend to library](/content/journals/cpd "Link to recommend this journal to a library")
  * [__Rights & Permissions](https://www.copyright.com/openurl?issn=1381-6128&contentIdType=doi&doi=10.2174%2F1381612829666230703161058 "Link to Reprints and Permissions page")
  * 


  1. [Home](/)
  2. [A-Z Publications](/content/publications)
  3. [Current Pharmaceutical Design](/content/journals/cpd)
  4. [ Volume 29, Issue 23 ](/content/journals/cpd/29/23)
  5. Article



  * Navigate this Journal 
  * [ About  ](/content/journals/cpd "About")
  * [ Current issue  ](/content/journals/cpd/browse "Current issue")
  * [ Previous issues  ](/content/journals/cpd/browse?page=previous-issues "Previous issues")
  * [ Early View  ](/content/journals/cpd/fasttrack "Early View")
  * [ Submit a paper  ](/content/journals/cpd?page=submit-a-paper "Submit a paper")
  * [ Contact the editor  ](/content/journals/cpd?page=contact-the-editor "Contact the editor")



[ ![Volume 29, Issue 23](/docserver/fulltext/cpd.jpg) ](/content/journals/cpd/29/23)

  * ISSN:  1381-6128 
  * E-ISSN:  1873-4286 



Buy this Article 

  * #  Novel Approaches to the Management of Diabetes Mellitus in Patients with Coronary Artery Disease 

  * **By** [Evangelos Oikonomou](/search?value1=Evangelos+Oikonomou&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Maria Xenou](/search?value1=Maria+Xenou&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [George E. Zakynthinos](/search?value1=George+E.+Zakynthinos&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Paraskevas Tsaplaris](/search?value1=Paraskevas+Tsaplaris&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Stamatios Lampsas](/search?value1=Stamatios+Lampsas&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Evanthia Bletsa](/search?value1=Evanthia+Bletsa&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Ioannis Gialamas](/search?value1=Ioannis+Gialamas&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Konstantinos Kalogeras](/search?value1=Konstantinos+Kalogeras&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Athina Goliopoulou](/search?value1=Athina+Goliopoulou&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Maria I. Gounaridi](/search?value1=Maria+I.+Gounaridi&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Theodoros Pesiridis](/search?value1=Theodoros+Pesiridis&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Aikaterini Tsatsaragkou](/search?value1=Aikaterini+Tsatsaragkou&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Manolis Vavouranakis](/search?value1=Manolis+Vavouranakis&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Gerasimos Siasos](/search?value1=Gerasimos+Siasos&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [Dimitris Tousoulis](/search?value1=Dimitris+Tousoulis&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)
  *   * **Source:** [Current Pharmaceutical Design](/content/journals/cpd), [Volume 29, Issue 23](/content/journals/cpd/29/23), Jun 2023, p. 1844 - 1862 
  * **DOI:** <https://doi.org/10.2174/1381612829666230703161058>
  *     * ****Available online** :** 01 Jun 2023 



  * [__Previous Article ](/content/journals/cpd/10.2174/1381612829666230601155001)
  * [Table of Contents](/content/journals/cpd/29/23)
  * [Next  Article  __](/content/journals/cpd/10.2174/1381612829666230807160956)



  * Abstract 

  * ______ **Abstract**
  * __**Metrics**
  * __**Related Content**



### Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with diabetes mellitus (DM). Although benefit has been attributed to the strict control of hyperglycemia with traditional antidiabetic treatments, novel antidiabetic medications have demonstrated cardiovascular (CV) safety and benefits by reducing major adverse cardiac events, improving heart failure (HF), and decreasing CVD-related mortality. Emerging data underline the interrelation between diabetes, as a metabolic disorder, and inflammation, endothelial dysfunction, and oxidative stress in the pathogenesis of microvascular and macrovascular complications. Conventional glucose-lowering medications demonstrate controversial CV effects. Dipeptidyl peptidase- 4 inhibitors have not only failed to prove to be beneficial in patients with coronary artery disease, but also their safety is questionable for the treatment of patients with CVD. However, metformin, as the first-line option for type 2 DM (T2DM), shows CVD protective properties for DM-induced atherosclerotic and macrovascular complications. Thiazolidinedione and sulfonylureas have questionable effects, as evidence from large studies shows a reduction in the risk of CV events and deaths, but with an increased rate of hospitalization for HF. Moreover, several studies have revealed that insulin monotherapy for T2DM treatment increases the risk of major CV events and deaths from HF, when compared to metformin, although it may reduce the risk of myocardial infarction. Finally, this review aimed to summarize the mechanisms of action of novel antidiabetic drugs acting as glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors that show favorable effects on blood pressure, lipid levels, and inflammation, leading to reduced CVD risk in T2DM patients.

(C) Bentham Science Publishers 

![Loading](/images/jp/spinner.gif)

Article metrics loading...

/content/journals/cpd/10.2174/1381612829666230703161058

2023-06-01

2025-02-28

  * ####  __From This Site

/content/journals/cpd/10.2174/1381612829666230703161058

dcterms_title,dcterms_subject,pub_keyword

-contentType:Contributor -contentType:Concept -contentType:Institution

10

5




Download as PowerPoint

![Loading full text...](/images/jp/spinner.gif)

Full text loading...

/content/journals/cpd/10.2174/1381612829666230703161058

![Loading](/images/jp/spinner.gif)

  * **  
Article Type:** Review Article 

**Keyword(s):** [antidiabetic drugs](/search?value1=%22antidiabetic+drugs%22&option1=pub_keyword "antidiabetic drugs"); [cardiovascular disease](/search?value1=%22cardiovascular+disease%22&option1=pub_keyword "cardiovascular disease"); [Diabetes mellitus](/search?value1=%22Diabetes+mellitus%22&option1=pub_keyword "Diabetes mellitus"); [GLP1RAs](/search?value1=%22GLP1RAs%22&option1=pub_keyword "GLP1RAs"); [pathophysiology](/search?value1=%22pathophysiology%22&option1=pub_keyword "pathophysiology"); [SGLT-2 inhibitors](/search?value1=%22SGLT-2+inhibitors%22&option1=pub_keyword "SGLT-2 inhibitors")

###  Most Read This Month 

Article

content/journals/cpd

Journal

5

3

false

en

![Loading](/images/jp/spinner.gif)

##  Most Cited  [ __ Most Cited RSS feed ](/rss/content/journals/cpd/mostcitedarticles?fmt=rss "Subscribe to most Cited RSS feed")

  *     * ###  [ Bioactive Proteins and Peptides from Food Sources. Applications of Bioprocesses used in Isolation and Recovery ](/content/journals/cpd/10.2174/1381612033454883)

Authors:  [D.D. Kitts](/search?value1=D.D.+Kitts&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [K. Weiler](/search?value1=K.+Weiler&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ Food-derived Bioactive Peptides - Opportunities for Designing Future Foods ](/content/journals/cpd/10.2174/1381612033454892)

Authors:  [H. Korhonen](/search?value1=H.+Korhonen&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [A. Pihlanto](/search?value1=A.+Pihlanto&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ Biofunctional Peptides from Milk Proteins: Mineral Binding and Cytomodulatory Effects ](/content/journals/cpd/10.2174/1381612033454847)

Authors:  [M. H.](/search?value1=M.+H.&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [F.R. J.](/search?value1=F.R.+J.&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ Induction of Cytoprotective Genes Through Nrf2 / Antioxidant Response Element Pathway: A New Therapeutic Approach for the Treatment of Inflammatory Diseases ](/content/journals/cpd/10.2174/1381612043452901)

Authors:  [Xi-Lin Chen](/search?value1=Xi-Lin+Chen&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [Charles Kunsch](/search?value1=Charles+Kunsch&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns? ](/content/journals/cpd/10.2174/1381612043383872)

Authors:  [Pal Pacher](/search?value1=Pal+Pacher&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [Valeria Kecskemeti](/search?value1=Valeria+Kecskemeti&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ The Urokinase Plasminogen Activator System: Role in Malignancy ](/content/journals/cpd/10.2174/1381612043453559)

By  [Michael J. Duffy](/search?value1=Michael+J.+Duffy&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ Insulin and the Blood-Brain Barrier ](/content/journals/cpd/10.2174/1381612033455323)

Authors:  [S.C. Woods](/search?value1=S.C.+Woods&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [R.J. Seeley](/search?value1=R.J.+Seeley&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [D.G. Baskin](/search?value1=D.G.+Baskin&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [M.W. Schwartz](/search?value1=M.W.+Schwartz&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ Imaging β-Amyloid Plaques and Neurofibrillary Tangles in the Aging Human Brain ](/content/journals/cpd/10.2174/1381612043384772)

Authors:  [C. A. Mathis](/search?value1=C.+A.+Mathis&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true), [Y. Wang](/search?value1=Y.+Wang&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [W. E. Klunk](/search?value1=W.+E.+Klunk&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ Membrane Disrupting Lytic Peptides for Cancer Treatments ](/content/journals/cpd/10.2174/1381612043383971)

Authors:  [Carola Leuschner](/search?value1=Carola+Leuschner&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true) and [William Hansel](/search?value1=William+Hansel&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  *     * ###  [ G-Quadruplex DNA as a Target for Drug Design ](/content/journals/cpd/10.2174/1381612003400849)

By  [S.M. Kerwin](/search?value1=S.M.+Kerwin&option1=author&noRedirect=true&sortField=prism_publicationDate&sortDescending=true)

  * __More __Less



###  __Access Key

  * s Titles Subscribed To
  * oa Open Access Content
  * t Free Trial Content
  * f Free Content



###   


  


  


  


### Bentham Science Content

  * [Journals](https://www.benthamdirect.com/content/journals)
  * [Books](https://www.benthamdirect.com/content/books)



### [**Editorial Board**](https://www.eurekaselect.com/journal/29/editorial-board)  
  


[Current Pharmaceutical Design editable blurb]()

__Back to top

### About

  *   
[About Us](https://eurekaselect.com/about-us)[  
](https://www.eurekaselect.com/pages/mission-statement-history)
  * [Mission Statement & History](https://www.eurekaselect.com/pages/mission-statement-history)
  * [Terms and Conditions](https://eurekaselect.com/terms-and-conditions)
  * [Contact Us](https://eurekaselect.com/contact-us)
  * Sitemap



### Publications

  * [A-Z index of journals](/content/publications "A-Z index of journals")
  * [Accredited journals ](/content/publications/?accredited=true "Read Journal of General Virology")
  * [Collections ](/content/collections "Collections ")
  * Open Access 
  * [Publishers](/content/publishers "Publishers")
  * [How to submit a paper](https://www.eurekaselect.com/pages/author-guidelines "How to submit a paper")



### Resources

  * [How to get access / subscribe](https://www.eurekaselect.com/order-subscription)
  * [Search Guide](/saepublications-search-guide "SA ePublications Search Guide")
  * [FAQ](https://www.eurekaselect.com/faq-reprint)
  * [Counter statistics](https://registry.projectcounter.org/platform/1dfece8a-433e-4a48-8764-55cd7adc7799)



  *   




Website (C) 2025 Bentham Science Publishers. All Rights reserved 

[ ![powered by ingenta](/images/instance/logo/poweredByIngentaLogo.png) ]( https://www.ingenta.com/products/content-management/ingenta-edify/)

This is a required field 

Please enter a valid email address 

Approval was a Success

Invalid data

An Error Occurred

Approval was partially successful, following selected items could not be processed due to error

Please enter a valid_number test

Bentham Science Publishers:

http://instance.metastore.ingenta.com/content/journals/cpd/10.2174/1381612829666230703161058

10.2174/1381612829666230703161058

SEARCH_EXPAND_ITEM

×

## Novel Approaches to the Management of Diabetes Mellitus in Patients with Coronary Artery Disease

**Publication Date:** 01 Jun 2023

<https://doi.org/10.2174/1381612829666230703161058>

1624369834

#### Online Option

Get immediate access to your online copy - available in PDF and ePub formats

Price: US$68.00

Buy Online Access

Cancel
  *[ ISSN: ]: International Standard Serial Number
  *[ E-ISSN: ]: Electronic International Standard Serial Number
  *[
**DOI:**]: Digital Object Identifier


url: http://arxiv.org/abs/2209.03448v1
scrape_date: 2025-02-28T16:46:40.971987
content_type: markdown
hash: fdada78a65c75b2bc46d7af6c10415a57ec4dd2766f422b91bb5de228806bf30
title:
[2209.03448v1] Designing an Optimized Electric Vehicle Charging Station Infrastructure for Urban Area: A Case study from Indonesia

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:2209.03448v1 

[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:2209.03448v1** (econ) 

[Submitted on 7 Sep 2022]

# Title:Designing an Optimized Electric Vehicle Charging Station Infrastructure for Urban Area: A Case study from Indonesia

Authors:[Nissa Amilia](https://arxiv.org/search/econ?searchtype=author&query=Amilia,+N), [Zulkifli Palinrungi](https://arxiv.org/search/econ?searchtype=author&query=Palinrungi,+Z), [Iwan Vanany](https://arxiv.org/search/econ?searchtype=author&query=Vanany,+I), [Mansur Arief](https://arxiv.org/search/econ?searchtype=author&query=Arief,+M)

View a PDF of the paper titled Designing an Optimized Electric Vehicle Charging Station Infrastructure for Urban Area: A Case study from Indonesia, by Nissa Amilia and 3 other authors

[View PDF](/pdf/2209.03448v1)

> Abstract:The rapid development of electric vehicle (EV) technologies promises cleaner air and more efficient transportation systems, especially for polluted and congested urban areas. To capitalize on this potential, the Indonesian government has appointed PLN, its largest state-owned electricity provider, to accelerate the preparation of Indonesia's EV infrastructure. With a mission of providing reliable, accessible, and cost-effective EV charging station infrastructure throughout the country, the company is prototyping a location-optimized model to simulate how well its infrastructure design reaches customers, fulfills demands, and generates revenue. In this work, we study how PLN could maximize profit by optimally placing EV charging stations in urban areas by adopting a maximal covering location model. In our experiments, we use data from Surabaya, Indonesia, and consider the two main transportation modes for the locals to charge: electric motorcycles and electric cars. Numerical experiments show that only four charging stations are needed to cover the whole city, given the charging technology that PLN has acquired. However, consumers' time-to-travel is exceptionally high (about 35 minutes), which could lead to poor consumer service and hindrance toward EV technologies. Sensitivity analysis reveals that building more charging stations could reduce the time but comes with higher costs due to extra facility installations. Adding layers of redundancy to buffer against outages or other disruptions also incurs higher costs but could be an appealing option to design a more reliable and thriving EV infrastructure. The model can provide insights to decision-makers to devise the most reliable and cost-effective infrastructure designs to support the deployment of electric vehicles and much more advanced intelligent transportation systems in the near future. 

Subjects: |  General Economics (econ.GN); Optimization and Control (math.OC)  
---|---  
Cite as: | [arXiv:2209.03448](https://arxiv.org/abs/2209.03448) [econ.GN]  
  | (or  [arXiv:2209.03448v1](https://arxiv.org/abs/2209.03448v1) [econ.GN] for this version)   
  |  <https://doi.org/10.48550/arXiv.2209.03448> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Mansur Arief [[view email](/show-email/ae3c2ea2/2209.03448)]   
**[v1]** Wed, 7 Sep 2022 20:10:51 UTC (2,730 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Designing an Optimized Electric Vehicle Charging Station Infrastructure for Urban Area: A Case study from Indonesia, by Nissa Amilia and 3 other authors

  * [View PDF](/pdf/2209.03448v1)
  * [TeX Source](/src/2209.03448v1)
  * [Other Formats](/format/2209.03448v1)



[view license](http://arxiv.org/licenses/nonexclusive-distrib/1.0/ "Rights to this article")

Current browse context: 

econ.GN

[< prev](/prevnext?id=2209.03448&function=prev&context=econ.GN "previous in econ.GN \(accesskey p\)")   |   [next >](/prevnext?id=2209.03448&function=next&context=econ.GN "next in econ.GN \(accesskey n\)")   


[new](/list/econ.GN/new) |  [recent](/list/econ.GN/recent) | [2022-09](/list/econ.GN/2022-09)

Change to browse by: 

[econ](/abs/2209.03448?context=econ)  
[math](/abs/2209.03448?context=math)  
[math.OC](/abs/2209.03448?context=math.OC)  
[q-fin](/abs/2209.03448?context=q-fin)  
[q-fin.EC](/abs/2209.03448?context=q-fin.EC)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2209.03448)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2209.03448)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2209.03448)



[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/2209.03448&description=Designing an Optimized Electric Vehicle Charging Station Infrastructure for Urban Area: A Case study from Indonesia "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2209.03448&title=Designing an Optimized Electric Vehicle Charging Station Infrastructure for Urban Area: A Case study from Indonesia "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/2209.03448) | [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)


scrape_date: 2025-02-28T16:46:41.091270
content_type: markdown
hash: f381fca2ed98d548fa1eeec39a9d73ff1021d5cd0a884dffcc4a98a4a8f8d4b3
url:
https://theicct.org/publication/a-global-comparison-of-the-life-cycle-greenhouse-gas-emissions-of-combustion-engine-and-electric-passenger-cars/

title:
A global comparison of the life-cycle greenhouse gas emissions of combustion engine and electric passenger cars - International Council on Clean Transportation

content:
[![ICCT 20 - Celebratoing 2 decades of clean transportation policy](https://theicct.org/wp-content/uploads/2025/02/20th-ICCT-logo-White-1.png)](https://theicct.org/)

  * [Donate](https://theicct.org/about/donate/)
  * [Press Room](https://theicct.org/about/press-room/)
  * [About](/about/)
    * [About the ICCT](/about/)
    * [Our Approach](https://theicct.org/about/our-approach/)
    * [Vision 2050](https://theicct.org/vision-2050/)
    * [Board of Directors](https://theicct.org/about/board-of-directors/)
    * [Staff](https://theicct.org/about/staff/)
    * [Locations](https://theicct.org/locations/)
    * [Equity at the ICCT](https://theicct.org/about/equity-at-the-icct/)
    * [Financials](https://theicct.org/about/financials/)
    * [Careers](https://theicct.org/about/careers/)



  * [Publications](/insight-analysis/publications/)
  * Short Reads
    * [Staff Blog](https://theicct.org/category/blog/)
    * [Market Spotlight](https://theicct.org/publication-type/market-spotlight/)
  * Regions & Transport
    *       *         * Regions
          * [Brazil](/region/brazil/)
          * [China](/region/china/)
          * [Europe](/region/europe/)
          * [India](/region/india/)
          * [Mexico](/region/mexico/)
          * [United States & Canada](/region/united-states-canada/)
          * [Africa & Middle East](/region/africa-middle-east/)
          * [Asia & Pacific](/region/asia-pacific/)
          * [Latin America](/region/latin-america/)
          * [Global](/region/global/)
          * [Cities](/region/cities/)
      *         * Transport
          * [Light vehicles](https://theicct.org/sector/light-vehicles/)
          * [Heavy vehicles](https://theicct.org/sector/heavy-vehicles/)
          * [Aviation](https://theicct.org/sector/aviation/)
          * [Maritime shipping](https://theicct.org/sector/maritime-shipping/)
          * [Fuels](https://theicct.org/sector/fuels/)
          * [Freight](https://theicct.org/sector/freight/)
  * [Resource Library](https://theicct.org/insight-analysis/)
    * [Events](https://theicct.org/events/)
    * [Explainers](https://theicct.org/insight-analysis/explainers/)
    * [Charts & Visualizations](https://theicct.org/insight-analysis/charts-visualizations/)
    * [Videos](https://theicct.org/insight-analysis/videos/)
    * [Tools for Policy & Research](https://theicct.org/tools-for-policy-and-research/)
    * [Browse by Topic](https://theicct.org/browse-by-topic/)
  * [Partnerships](https://theicct.org/partnerships/)
  * [Donate](https://theicct.org/about/donate/)
  * [Press room](https://theicct.org/about/press-room/)
  * [About](https://theicct.org/about/)
    * [Our Approach](https://theicct.org/about/our-approach/)
    * [Vision 2050](https://theicct.org/vision-2050/)
    * [Board of Directors](https://theicct.org/about/board-of-directors/)
    * [Staff](https://theicct.org/about/staff/)
    * [Locations](https://theicct.org/locations/)
    * [Equity at the ICCT](https://theicct.org/about/equity-at-the-icct/)
    * [Financials](https://theicct.org/about/financials/)
    * [Careers](https://theicct.org/about/careers/)
  * [Search](https://theicct.org/search/)



Search for:

White paper 

# A global comparison of the life-cycle greenhouse gas emissions of combustion engine and electric passenger cars

July 20, 2021 | By: Georg Bieker

[Download](https://theicct.org/wp-content/uploads/2021/07/Global-Vehicle-LCA-White-Paper-A4-revised-v2.pdf)

This wide-ranging life-cycle assessment (LCA) examines the greenhouse gas (GHG) emissions of passenger cars, including SUVs. Performed separately and in depth for Europe, the United States, China, and India, the analysis captures the differences among those markets, which are home to about 70% of global new passenger car sales. It considers present and projected future GHG emissions attributable to every stage in the life cycles of both vehicles and fuels, from extracting and processing raw materials through refining and manufacture to operation and eventual recycling or disposal.

In addition to its global scope, the study is methodologically comprehensive in considering all relevant powertrain types, including plug-in hybrid electric vehicles (PHEVs), and an array of fuel types including biofuels, electrofuels, hydrogen, and electricity. The life-cycle GHG emissions of cars registered in 2021 are compared with those of cars expected to be registered in 2030. In addition, this study is distinct from earlier LCA literature in four key aspects:

  * It considers the lifetime average carbon intensity of the fuel and electricity mixes, including biofuels and biogas. Based on stated policies, it accounts for changes in the carbon intensity during the useful lifetime of the vehicles.
  * It considers the fuel and electricity consumption in average real-world usage instead of solely relying on official test values. This is especially important for assessing the GHG emissions of PHEVs.
  * It uses recent data on industrial-scale battery production and considers regional battery supply chains. This results in significantly lower battery production emissions than in earlier studies.
  * It incorporates the near-term global warming potential of methane leakage emissions of natural gas and natural gas-derived hydrogen pathways. Different from other GHGs, methane contributes several times more to global warming in the first 20 years after emission than is reflected by the 100-year global warming potential.



Results show that even for cars registered today, battery electric vehicles (BEVs) have by far the lowest life-cycle GHG emissions. As illustrated in the figure below, emissions over the lifetime of average medium-size BEVs registered today are already lower than comparable gasoline cars by 66%–69% in Europe, 60%–68% in the United States, 37%–45% in China, and 19%–34% in India. Additionally, as the electricity mix continues to decarbonize, the life-cycle emissions gap between BEVs and gasoline vehicles increases substantially when considering medium-size cars projected to be registered in 2030.

Highlights of the paper are in the fact sheets attached below, one covering the full scope of the analysis and the other, in German, focused on Europe. See [here](//theicct.org/publications/eu-co2-FS6-jul2021) for the Europe-focused fact sheet in English. This work is also incorporated in a [briefing](//theicct.org/publications/zevtc-decarbonizing-by-2050-jul2021) that’s part of our work with the [Zero Emission Vehicles Transition Council](/initiatives-partnerships/zev-tc/).

![Figure](data:image/gif;base64,R0lGODlhAQABAAAAACH5BAEKAAEALAAAAAABAAEAAAICTAEAOw==)

_This paper was updated on November 11, 2022, to correct electricity mix values for certain countries in the European country-specific sensitivity in Figure 3.5._

**Attachments**  
[Global-LCA-passenger-cars-FS-EN-jul2021.pdf](https://theicct.org/wp-content/uploads/2022/01/Global-LCA-passenger-cars-FS-EN-jul2021.pdf)  
[Global-LCA-passenger-cars-FS-DE-jul2021.pdf](https://theicct.org/wp-content/uploads/2022/01/Global-LCA-passenger-cars-FS-DE-jul2021.pdf)  
[Global-LCA-passenger-cars-PR-jul2021.pdf](https://theicct.org/wp-content/uploads/2022/01/Global-LCA-passenger-cars-PR-jul2021.pdf)  


[Download](https://theicct.org/wp-content/uploads/2021/07/Global-Vehicle-LCA-White-Paper-A4-revised-v2.pdf)

Decarbonizing Transport [Alternative fuels](/decarbonizing/alternative-fuels) [Electrification](/decarbonizing/electrification) [Life-cycle analyses](/decarbonizing/life-cycle-analyses) [Zero-emission vehicles](/decarbonizing/zero-emission-vehicles)

Sector [Fuels](/sector/fuels) [Light vehicles](/sector/light-vehicles)

Policies [Fuels](/policies/fuels) [GHG emissions](/policies/ghg-emissions)

Region [China](/region/china) [Europe](/region/europe) [India](/region/india) [United States & Canada](/region/united-states-canada)

## Related Content

[ZEVTC publication](https://theicct.org/publication-type/zevtc-publication/)

[Decarbonizing road transport by 2050: Zero-emission pathways for passenger vehicles](https://theicct.org/publication/decarbonizing-road-transport-by-2050-zero-emission-pathways-for-passenger-vehicles/)

July 20, 2021

[White paper](https://theicct.org/publication-type/white-paper/)

[How technology, recycling, and policy can mitigate supply risks to the long-term transition to zero-emission vehicles](https://theicct.org/publication/how-technology-recycling-and-policy-can-mitigate-supply-risks-to-the-long-term-transition-to-zero-emission-vehicles/)

December 8, 2020

[Blog](https://theicct.org/category/blog/)

[Why are electric vehicles the only way to quickly and substantially decarbonize transport?](https://theicct.org/why-are-electric-vehicles-the-only-way-to-quickly-and-substantially-decarbonize-transport/)

July 21, 2021

[Video](https://theicct.org/category/video/)

[Electric Vehicles – a Win Win for Consumers and the Climate](https://theicct.org/webr-evs-icct-cr-dec21/)

December 20, 2021

Join our [mailing list](/newsletter) to keep up with ICCT's latest research and analysis.

 

  * [Twitter](https://twitter.com/theicct)
  * [YouTube](https://www.youtube.com/user/CleanTransport)
  * [LinkedIn](https://www.linkedin.com/company/the-international-council-on-clean-transportation)
  * [Bluesky](https://bsky.app/profile/theicct.org)



[Contact Us](/contact-us)

(C) 2025 International Council on Clean Transportation. All Rights Reserved. [Privacy Policy](/privacy) / [Legal](/legal) / [Sitemap](/sitemap) / [Web Development by Boxcar Studio](https://boxcarstudio.com)

We use cookies to improve site functionality and make this website more useful to visitors. [Find out more](https://theicct.org/privacy).

Accept Settings

  * Privacy Overview
  * Essential Cookies
  * Analytics



Privacy Overview

![International Council on Clean Transportation](data:image/gif;base64,R0lGODlhAQABAAAAACH5BAEKAAEALAAAAAABAAEAAAICTAEAOw==)

This website uses cookies to enable some basic functionality and also to help us understand how visitors use the site, so that we can improve it.

Essential Cookies

Essential cookies provide basic core functionality, such as saving user preferences. You can disable these cookies in your browser settings.

Enable or Disable Cookies

Analytics

We use Google Analytics to collect anonymous information about how visitors interact with this website and the information we provide here, so that we can improve both over the long run. For more on how we use this information please see our privacy policy.

Enable or Disable Cookies

Accept and Save

[Powered by  GDPR Cookie Compliance](https://wordpress.org/plugins/gdpr-cookie-compliance/)


url: http://arxiv.org/abs/2403.16830v1
scrape_date: 2025-02-28T17:02:48.244590
content_type: markdown
hash: f0a22a6ea95fe92dd2813fb8b47f592ff238aa476e9ddebf5d9558227a3e4a65
title:
[2403.16830v1] Exploring Communication Technologies, Standards, and Challenges in Electrified Vehicle Charging

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)](/) > [cs](/list/cs/recent) > arXiv:2403.16830v1 

[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)



# Computer Science > Networking and Internet Architecture

**arXiv:2403.16830v1** (cs) 

[Submitted on 25 Mar 2024]

# Title:Exploring Communication Technologies, Standards, and Challenges in Electrified Vehicle Charging

Authors:[Xiang Ma](https://arxiv.org/search/cs?searchtype=author&query=Ma,+X), [Yuan Zhou](https://arxiv.org/search/cs?searchtype=author&query=Zhou,+Y), [Hanwen Zhang](https://arxiv.org/search/cs?searchtype=author&query=Zhang,+H), [Qun Wang](https://arxiv.org/search/cs?searchtype=author&query=Wang,+Q), [Haijian Sun](https://arxiv.org/search/cs?searchtype=author&query=Sun,+H), [Hongjie Wang](https://arxiv.org/search/cs?searchtype=author&query=Wang,+H), [Rose Qingyang Hu](https://arxiv.org/search/cs?searchtype=author&query=Hu,+R+Q)

View a PDF of the paper titled Exploring Communication Technologies, Standards, and Challenges in Electrified Vehicle Charging, by Xiang Ma and 6 other authors

[View PDF](/pdf/2403.16830v1) [HTML (experimental)](https://arxiv.org/html/2403.16830v1)

> Abstract:As public awareness of environmental protection continues to grow, the trend of integrating more electric vehicles (EVs) into the transportation sector is rising. Unlike conventional internal combustion engine (ICE) vehicles, EVs can minimize carbon emissions and potentially achieve autonomous driving. However, several obstacles hinder the widespread adoption of EVs, such as their constrained driving range and the extended time required for charging. One alternative solution to address these challenges is implementing dynamic wireless power transfer (DWPT), charging EVs in motion on the road. Moreover, charging stations with static wireless power transfer (SWPT) infrastructure can replace existing gas stations, enabling users to charge EVs in parking lots or at home. This paper surveys the communication infrastructure for static and dynamic wireless charging in electric vehicles. It encompasses all communication aspects involved in the wireless charging process. The architecture and communication requirements for static and dynamic wireless charging are presented separately. Additionally, a comprehensive comparison of existing communication standards is provided. The communication with the grid is also explored in detail. The survey gives attention to security and privacy issues arising during communications. In summary, the paper addresses the challenges and outlines upcoming trends in communication for EV wireless charging. 

Comments: | submitted to IET Communication as a survey paper  
---|---  
Subjects: |  Networking and Internet Architecture (cs.NI); Signal Processing (eess.SP)  
Cite as: | [arXiv:2403.16830](https://arxiv.org/abs/2403.16830) [cs.NI]  
  | (or  [arXiv:2403.16830v1](https://arxiv.org/abs/2403.16830v1) [cs.NI] for this version)   
  |  <https://doi.org/10.48550/arXiv.2403.16830> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Haijian Sun [[view email](/show-email/bad19dab/2403.16830)]   
**[v1]** Mon, 25 Mar 2024 14:56:14 UTC (1,808 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Exploring Communication Technologies, Standards, and Challenges in Electrified Vehicle Charging, by Xiang Ma and 6 other authors

  * [View PDF](/pdf/2403.16830v1)
  * [HTML (experimental)](https://arxiv.org/html/2403.16830v1)
  * [TeX Source](/src/2403.16830v1)
  * [Other Formats](/format/2403.16830v1)



[ ![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: 

cs.NI

[< prev](/prevnext?id=2403.16830&function=prev&context=cs.NI "previous in cs.NI \(accesskey p\)")   |   [next >](/prevnext?id=2403.16830&function=next&context=cs.NI "next in cs.NI \(accesskey n\)")   


[new](/list/cs.NI/new) |  [recent](/list/cs.NI/recent) | [2024-03](/list/cs.NI/2024-03)

Change to browse by: 

[cs](/abs/2403.16830?context=cs)  
[eess](/abs/2403.16830?context=eess)  
[eess.SP](/abs/2403.16830?context=eess.SP)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2403.16830)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2403.16830)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2403.16830)



[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/2403.16830&description=Exploring Communication Technologies, Standards, and Challenges in Electrified Vehicle Charging "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2403.16830&title=Exploring Communication Technologies, Standards, and Challenges in Electrified Vehicle Charging "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/2403.16830) | [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/1612.07568v2
title: [1612.07568v2] Pedestrian-Aware Engine Management Strategies for Plug-in Hybrid Electric Vehicles
scrape_date: 2025-02-28T17:02:48.284266
content_type: markdown
hash: 1af28da417700d5063f4887e534aa8905b4c758a05f2b90a72dc3391b57e1814
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)](/) > [cs](/list/cs/recent) > arXiv:1612.07568v2 

[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)



# Computer Science > Systems and Control

**arXiv:1612.07568v2** (cs) 

[Submitted on 22 Dec 2016 ([v1](https://arxiv.org/abs/1612.07568v1)), last revised 6 Apr 2017 (this version, v2)]

# Title:Pedestrian-Aware Engine Management Strategies for Plug-in Hybrid Electric Vehicles

Authors:[Yingqi Gu](https://arxiv.org/search/cs?searchtype=author&query=Gu,+Y), [Mingming Liu](https://arxiv.org/search/cs?searchtype=author&query=Liu,+M), [Joe Naoum-Sawaya](https://arxiv.org/search/cs?searchtype=author&query=Naoum-Sawaya,+J), [Emanuele Crisostomi](https://arxiv.org/search/cs?searchtype=author&query=Crisostomi,+E), [Giovanni Russo](https://arxiv.org/search/cs?searchtype=author&query=Russo,+G), [Robert Shorten](https://arxiv.org/search/cs?searchtype=author&query=Shorten,+R)

View a PDF of the paper titled Pedestrian-Aware Engine Management Strategies for Plug-in Hybrid Electric Vehicles, by Yingqi Gu and 5 other authors

[View PDF](/pdf/1612.07568v2)

> Abstract:Electric Vehicles (EVs) and Plug-in Hybrid Electric Vehicles (PHEVs) are increasingly being seen as a means of mitigating the pressing concerns of traffic-related pollution. While hybrid vehicles are usually designed with the objective of minimising fuel consumption, in this paper we propose engine management strategies that also take into account environmental effects of the vehicles to pedestrians outside of the vehicles. Specifically, we present optimisation based engine energy management strategies for PHEVs, that attempt to minimise the environmental impact of pedestrians along the route of the vehicle, while taking account of route dependent uncertainties. We implement the proposed approach in a real PHEV, and evaluate the performance in a hardware-in-the-loop platform. A variety of simulation results are given to illustrate the efficacy of our proposed approach. 

Subjects: |  Systems and Control (eess.SY)  
---|---  
Cite as: | [arXiv:1612.07568](https://arxiv.org/abs/1612.07568) [cs.SY]  
  | (or  [arXiv:1612.07568v2](https://arxiv.org/abs/1612.07568v2) [cs.SY] for this version)   
  |  <https://doi.org/10.48550/arXiv.1612.07568> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Mingming Liu [[view email](/show-email/a78c4350/1612.07568)]   
**[[v1]](/abs/1612.07568v1)** Thu, 22 Dec 2016 12:20:21 UTC (3,526 KB)  
**[v2]** Thu, 6 Apr 2017 11:30:42 UTC (3,826 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Pedestrian-Aware Engine Management Strategies for Plug-in Hybrid Electric Vehicles, by Yingqi Gu and 5 other authors

  * [View PDF](/pdf/1612.07568v2)
  * [TeX Source](/src/1612.07568v2)
  * [Other Formats](/format/1612.07568v2)



[ ![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: 

eess.SY

[< prev](/prevnext?id=1612.07568&function=prev&context=eess.SY "previous in eess.SY \(accesskey p\)")   |   [next >](/prevnext?id=1612.07568&function=next&context=eess.SY "next in eess.SY \(accesskey n\)")   


[new](/list/eess.SY/new) |  [recent](/list/eess.SY/recent) | [2016-12](/list/eess.SY/2016-12)

Change to browse by: 

[cs](/abs/1612.07568?context=cs)  
[cs.SY](/abs/1612.07568?context=cs.SY)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:1612.07568)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=1612.07568)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:1612.07568)



### [DBLP](https://dblp.uni-trier.de) \- CS Bibliography

[listing](https://dblp.uni-trier.de/db/journals/corr/corr1612.html#GuLNCRS16 "listing on DBLP") | [bibtex](https://dblp.uni-trier.de/rec/bibtex/journals/corr/GuLNCRS16 "DBLP bibtex record")

[Yingqi Gu](https://dblp.uni-trier.de/search/author?author=Yingqi%20Gu "DBLP author search")  
[Mingming Liu](https://dblp.uni-trier.de/search/author?author=Mingming%20Liu "DBLP author search")  
[Joe Naoum-Sawaya](https://dblp.uni-trier.de/search/author?author=Joe%20Naoum-Sawaya "DBLP author search")  
[Emanuele Crisostomi](https://dblp.uni-trier.de/search/author?author=Emanuele%20Crisostomi "DBLP author search")  
[Giovanni Russo](https://dblp.uni-trier.de/search/author?author=Giovanni%20Russo "DBLP author search")

…

[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/1612.07568&description=Pedestrian-Aware Engine Management Strategies for Plug-in Hybrid Electric Vehicles "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/1612.07568&title=Pedestrian-Aware Engine Management Strategies for Plug-in Hybrid Electric Vehicles "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/1612.07568) | [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/2502.09779v1
scrape_date: 2025-02-28T17:08:52.822159
content_type: markdown
hash: e51285bffa2979fcabd1524e63ea3355a2fcd9ad6f4183ee59678cc93c86c779
title:
[2502.09779v1] Automated Muscle and Fat Segmentation in Computed Tomography for Comprehensive Body Composition Analysis

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:2502.09779v1 

[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 > Image and Video Processing

**arXiv:2502.09779v1** (eess) 

[Submitted on 13 Feb 2025]

# Title:Automated Muscle and Fat Segmentation in Computed Tomography for Comprehensive Body Composition Analysis

Authors:[Yaqian Chen](https://arxiv.org/search/eess?searchtype=author&query=Chen,+Y), [Hanxue Gu](https://arxiv.org/search/eess?searchtype=author&query=Gu,+H), [Yuwen Chen](https://arxiv.org/search/eess?searchtype=author&query=Chen,+Y), [Jicheng Yang](https://arxiv.org/search/eess?searchtype=author&query=Yang,+J), [Haoyu Dong](https://arxiv.org/search/eess?searchtype=author&query=Dong,+H), [Joseph Y. Cao](https://arxiv.org/search/eess?searchtype=author&query=Cao,+J+Y), [Adrian Camarena](https://arxiv.org/search/eess?searchtype=author&query=Camarena,+A), [Christopher Mantyh](https://arxiv.org/search/eess?searchtype=author&query=Mantyh,+C), [Roy Colglazier](https://arxiv.org/search/eess?searchtype=author&query=Colglazier,+R), [Maciej A. Mazurowski](https://arxiv.org/search/eess?searchtype=author&query=Mazurowski,+M+A)

View a PDF of the paper titled Automated Muscle and Fat Segmentation in Computed Tomography for Comprehensive Body Composition Analysis, by Yaqian Chen and 9 other authors

[View PDF](/pdf/2502.09779v1) [HTML (experimental)](https://arxiv.org/html/2502.09779v1)

> Abstract:Body composition assessment using CT images can potentially be used for a number of clinical applications, including the prognostication of cardiovascular outcomes, evaluation of metabolic health, monitoring of disease progression, assessment of nutritional status, prediction of treatment response in oncology, and risk stratification for surgical and critical care outcomes. While multiple groups have developed in-house segmentation tools for this analysis, there are very limited publicly available tools that could be consistently used across different applications. To mitigate this gap, we present a publicly accessible, end-to-end segmentation and feature calculation model specifically for CT body composition analysis. Our model performs segmentation of skeletal muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) across the chest, abdomen, and pelvis area in axial CT images. It also provides various body composition metrics, including muscle density, visceral-to-subcutaneous fat (VAT/SAT) ratio, muscle area/volume, and skeletal muscle index (SMI), supporting both 2D and 3D assessments. The model is shared for public use. To evaluate the model, the segmentation was applied to both internal and external datasets, with body composition metrics analyzed across different age, sex, and race groups. The model achieved high dice coefficients on both internal and external datasets, exceeding 89% for skeletal muscle, SAT, and VAT segmentation. The model outperforms the benchmark by 2.40% on skeletal muscle and 10.26% on SAT compared to the manual annotations given by the publicly available dataset. Body composition metrics show mean relative absolute errors (MRAEs) under 10% for all measures. Furthermore, the model provided muscular fat segmentation with a Dice coefficient of 56.27%, which can be utilized for additional analyses as needed. 

Subjects: |  Image and Video Processing (eess.IV); Computer Vision and Pattern Recognition (cs.CV)  
---|---  
Cite as: | [arXiv:2502.09779](https://arxiv.org/abs/2502.09779) [eess.IV]  
  | (or  [arXiv:2502.09779v1](https://arxiv.org/abs/2502.09779v1) [eess.IV] for this version)   
  |  <https://doi.org/10.48550/arXiv.2502.09779> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Yaqian Chen [[view email](/show-email/c2727911/2502.09779)]   
**[v1]** Thu, 13 Feb 2025 21:27:10 UTC (18,098 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Automated Muscle and Fat Segmentation in Computed Tomography for Comprehensive Body Composition Analysis, by Yaqian Chen and 9 other authors

  * [View PDF](/pdf/2502.09779v1)
  * [HTML (experimental)](https://arxiv.org/html/2502.09779v1)
  * [TeX Source](/src/2502.09779v1)
  * [Other Formats](/format/2502.09779v1)



[ ![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: 

eess.IV

[< prev](/prevnext?id=2502.09779&function=prev&context=eess.IV "previous in eess.IV \(accesskey p\)")   |   [next >](/prevnext?id=2502.09779&function=next&context=eess.IV "next in eess.IV \(accesskey n\)")   


[new](/list/eess.IV/new) |  [recent](/list/eess.IV/recent) | [2025-02](/list/eess.IV/2025-02)

Change to browse by: 

[cs](/abs/2502.09779?context=cs)  
[cs.CV](/abs/2502.09779?context=cs.CV)  
[eess](/abs/2502.09779?context=eess)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2502.09779)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2502.09779)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2502.09779)



[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/2502.09779&description=Automated Muscle and Fat Segmentation in Computed Tomography for Comprehensive Body Composition Analysis "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2502.09779&title=Automated Muscle and Fat Segmentation in Computed Tomography for Comprehensive Body Composition Analysis "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/2502.09779) | [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://pmc.ncbi.nlm.nih.gov/articles/PMC10965408/
scrape_date: 2025-02-28T17:08:52.983988
content_type: markdown
hash: 9f8471e718f8d96bec112dfc4b50e647a7cde81283abe45bd87f6f8d5fb397ab
title:
            Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial - 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/10.1016/j.eclinm.2024.102475 "View on publisher site")
  * [ ](pdf/main.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/)

![eClinicalMedicine logo](https://cdn.ncbi.nlm.nih.gov/pmc/banners/logo-eclinm.jpg)

eClinicalMedicine

. 2024 Feb 19;69:102475. doi: [10.1016/j.eclinm.2024.102475](https://doi.org/10.1016/j.eclinm.2024.102475)

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



# Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial

[Simon Birk Kjær Jensen](https://pubmed.ncbi.nlm.nih.gov/?term=%22Jensen%20SBK%22%5BAuthor%5D)

### Simon Birk Kjær Jensen

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Find articles by [Simon Birk Kjær Jensen](https://pubmed.ncbi.nlm.nih.gov/?term=%22Jensen%20SBK%22%5BAuthor%5D)

a, [Martin Bæk Blond](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blond%20MB%22%5BAuthor%5D)

### Martin Bæk Blond

bSteno Diabetes Center Copenhagen, Herlev, Denmark

Find articles by [Martin Bæk Blond](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blond%20MB%22%5BAuthor%5D)

b, [Rasmus Michael Sandsdal](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sandsdal%20RM%22%5BAuthor%5D)

### Rasmus Michael Sandsdal

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Find articles by [Rasmus Michael Sandsdal](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sandsdal%20RM%22%5BAuthor%5D)

a, [Lisa Møller Olsen](https://pubmed.ncbi.nlm.nih.gov/?term=%22Olsen%20LM%22%5BAuthor%5D)

### Lisa Møller Olsen

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Find articles by [Lisa Møller Olsen](https://pubmed.ncbi.nlm.nih.gov/?term=%22Olsen%20LM%22%5BAuthor%5D)

a, [Christian Rimer Juhl](https://pubmed.ncbi.nlm.nih.gov/?term=%22Juhl%20CR%22%5BAuthor%5D)

### Christian Rimer Juhl

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Find articles by [Christian Rimer Juhl](https://pubmed.ncbi.nlm.nih.gov/?term=%22Juhl%20CR%22%5BAuthor%5D)

a, [Julie Rehné Lundgren](https://pubmed.ncbi.nlm.nih.gov/?term=%22Lundgren%20JR%22%5BAuthor%5D)

### Julie Rehné Lundgren

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Find articles by [Julie Rehné Lundgren](https://pubmed.ncbi.nlm.nih.gov/?term=%22Lundgren%20JR%22%5BAuthor%5D)

a, [Charlotte Janus](https://pubmed.ncbi.nlm.nih.gov/?term=%22Janus%20C%22%5BAuthor%5D)

### Charlotte Janus

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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

a, [Bente Merete Stallknecht](https://pubmed.ncbi.nlm.nih.gov/?term=%22Stallknecht%20BM%22%5BAuthor%5D)

### Bente Merete Stallknecht

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Find articles by [Bente Merete Stallknecht](https://pubmed.ncbi.nlm.nih.gov/?term=%22Stallknecht%20BM%22%5BAuthor%5D)

a, [Jens Juul Holst](https://pubmed.ncbi.nlm.nih.gov/?term=%22Holst%20JJ%22%5BAuthor%5D)

### Jens Juul Holst

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

cNNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

Find articles by [Jens Juul Holst](https://pubmed.ncbi.nlm.nih.gov/?term=%22Holst%20JJ%22%5BAuthor%5D)

a,c, [Sten Madsbad](https://pubmed.ncbi.nlm.nih.gov/?term=%22Madsbad%20S%22%5BAuthor%5D)

### Sten Madsbad

dDepartment of Endocrinology, Copenhagen University Hospital – Hvidovre, Hvidovre, Denmark

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

d, [Signe Sørensen Torekov](https://pubmed.ncbi.nlm.nih.gov/?term=%22Torekov%20SS%22%5BAuthor%5D)

### Signe Sørensen Torekov

aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Find articles by [Signe Sørensen Torekov](https://pubmed.ncbi.nlm.nih.gov/?term=%22Torekov%20SS%22%5BAuthor%5D)

a,∗

  * Author information
  * Article notes
  * Copyright and License information



aDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

bSteno Diabetes Center Copenhagen, Herlev, Denmark

cNNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

dDepartment of Endocrinology, Copenhagen University Hospital – Hvidovre, Hvidovre, Denmark

∗

Corresponding author. Department of Biomedical Sciences, University of Copenhagen, Copenhagen N, DK-2200, Denmark. torekov@sund.ku.dk

Received 2023 Oct 17; Revised 2024 Jan 24; Accepted 2024 Jan 24; Collection date 2024 Mar.

© 2024 The Authors

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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

PMCID: PMC10965408 PMID: [38544798](https://pubmed.ncbi.nlm.nih.gov/38544798/)

## Summary

### Background

New obesity medications result in large weight losses. However, long-term adherence in a real-world setting is challenging, and termination of obesity medication results in weight regain towards pre-treatment body weight. Therefore, we investigated whether weight loss and improved body composition are sustained better at 1 year after termination of active treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, supervised exercise program, or both combined for 1 year.

### Methods

We conducted a post-treatment study in extension of a randomised, controlled trial in Copenhagen. Adults with obesity (aged 18–65 years and initial body mass index 32–43 kg/m2) completed an eight-week low-calorie diet-induced weight loss of 13.1 kg (week −8 to 0) and were randomly allocated (1:1:1:1) to one-year weight loss maintenance (week 0–52) with either supervised exercise, the GLP-1 receptor agonist once-daily subcutaneous liraglutide 3.0 mg, the combination of exercise and liraglutide, or placebo. 166 Participants completed the weight loss maintenance phase. All randomised participants were invited to participate in the post-treatment study with outcome assessments one year after treatment termination, at week 104. The primary outcome of the post-treatment assessment was change in body weight from after the initial weight loss (at randomisation, week 0) to one year after treatment termination (week 104) in the intention-to-treat population. The secondary outcome was change in body-fat percentage (week 0–104). The study is registered with EudraCT, 2015-005585-32, and with [ClinicalTrials.gov](http://ClinicalTrials.gov), [NCT04122716](https://clinicaltrials.gov/ct2/show/NCT04122716).

### Findings

Between Dec 17, 2018, and Dec 17, 2020, 109 participants attended the post-treatment study. From randomisation to one year after termination of combined exercise and liraglutide treatment (week 0–104), participants had reduced body weight (−5.1 kg [95% CI −10.0; −0.2]; P = 0.040) and body-fat percentage (−2.3%-points [−4.3 to −0.3]; P = 0.026) compared with after termination of liraglutide alone. More participants who had previously received combination treatment maintained a weight loss of at least 10% of initial body weight one year after treatment termination (week −8 to 104) compared with participants who had previously received placebo (odds ratio [OR] 7.2 [2.4; 21.3]) and liraglutide (OR 4.2 [1.6; 10.8]). More participants who had previously received supervised exercise maintained a weight loss of at least 10% compared with placebo (OR 3.7 [1.2; 11.1]). During the year after termination of treatment (week 52–104), weight regain was 6.0 kg [2.1; 10.0] larger after termination of liraglutide compared with after termination of supervised exercise and 2.5 kg [−1.5 to 6.5] compared with after termination of combination treatment.

### Interpretation

The addition of supervised exercise to obesity pharmacotherapy seems to improve healthy weight maintenance after treatment termination compared with treatment termination of obesity pharmacotherapy alone. Body weight and body composition were maintained one year after termination of supervised exercise, in contrast to weight regain after termination of treatment with obesity pharmacotherapy alone.

### Funding

Helsefonden and the Novo Nordisk Foundation.

**Keywords:** Obesity, Weight loss maintenance, GLP-1 receptor agonist, Exercise, Physical activity

* * *

## Research in context.

### Evidence before this study

Newly developed incretin-based obesity pharmacotherapies result in marked weight loss. However, in real-world settings, up to half of those who initiate incretin-based therapy, have discontinued treatment within the first year. We searched PubMed for randomised controlled trials with exercise and/or pharmaceutical treatment of overweight/obesity and a post-treatment phase until September 6, 2023, with the search terms: (“exercise” OR “physical activity”) OR (“glucagon-like peptide-1 receptor agonist∗” OR “liraglutide” OR “semaglutide” OR “tirzepatide”) AND (“follow-up” OR “extension” OR “post-treatment” OR “post treatment” OR “off-treatment” OR “off treatment” OR “termination” OR “discontinuation” OR “withdrawal” OR “after treatment”) AND (“overweight” OR “obesity” OR “weight loss” OR “weight maintenance”). An off-treatment extension of a study of semaglutide, a receptor agonist of the incretin glucagon-like peptide-1 (GLP-1), showed that about two-thirds of the lost weight was regained within the first year after treatment termination. In contrast, most studies on physical activity treatment programs have reported sustained increases in physical activity levels after termination of the supervised program. In a randomised controlled trial, the combination of supervised exercise program and the GLP-1 receptor agonist liraglutide was superior to the separate treatments in terms of healthy weight loss maintenance. No studies have investigated whether improved body weight and body composition are maintained differently after the termination of a treatment regimen with exercise, pharmacotherapy, or both combined.

### Added value of this study

In this study, we investigated whether weight loss and improved body composition were preserved better at 1 year after termination of active treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, supervised exercise program, or both combined for 1 year. One year after treatment termination, participants who had previously received combined supervised exercise and GLP-1 receptor agonist treatment had maintained weight loss and body-fat reduction, in contrast to weight regain for participants who had previously received GLP-1 receptor agonist alone. More participants who had previously received combination treatment maintained weight losses of at least 10% one year after treatment termination compared with participants who had received placebo or GLP-1 receptor agonist alone. Weight regain during the one-year post-treatment phase was 6 kg larger after GLP-1 receptor agonist treatment compared with after supervised exercise. These results indicate that incorporating supervised exercise together with obesity pharmacotherapy helps preserve the improved body weight and body composition after termination of obesity pharmacotherapy.

### Implications of all the available evidence

All available evidence shows that weight loss obtained with obesity pharmacotherapy is challenging to maintain after termination of treatment. Supervised exercise together with obesity pharmacotherapy holds more potential for preventing body weight and fat mass regain after treatment termination compared with obesity pharmacotherapy without supervised exercise.

## Introduction

Obesity is a chronic and relapsing condition associated with numerous complications, including cardiovascular disease, type 2 diabetes, and impaired quality of life.1, 2, 3, 4

Incretin-based treatments such as glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of obesity and type 2 diabetes. GLP-1 receptor agonists induce weight loss primarily due to reduced appetite and, consequently, reduced food intake.5,6 The S-LiTE study (Synergy effect of the appetite hormone GLP-1 (LiragluTide) and Exercise on maintenance of weight loss and health after a low-calorie diet) demonstrated superiority of the GLP-1 receptor agonist liraglutide combined with a supervised exercise program for weight maintenance and improved body composition after weight loss compared with the single treatments.7

New incretin-based obesity medications have shown significant therapeutic potential. The GLP-1 receptor agonist, semaglutide, resulted in 12% larger weight loss than placebo after 68 weeks.8 The GLP-1 and glucose-dependent insulinotropic polypeptide co-agonist, tirzepatide, resulted in 18% weight loss compared with placebo after 78 weeks.9 Despite the large weight losses with obesity medications, long-term adherence in a real-world setting is challenging since the medications are expensive and gastrointestinal adverse events are common.8,10,11 The longest controlled trials of GLP-1 receptor agonist usage are 3–4 years,12,13 and the long-term effects beyond this time are not well-described. In real-world settings, up to half of those who initiate treatment with a GLP-1 receptor agonist have discontinued treatment after one year.14, 15, 16, 17 Switching to placebo after 20 weeks of semaglutide treatment resulted in a weight regain of 6.9% body weight in contrast to a weight reduction of 7.9% body weight with continuous semaglutide treatment at week 68, despite monthly recommendations of calorie-reduced diet and increased physical activity.18 During a one-year off-treatment period in extension of 68 weeks of semaglutide treatment, two-thirds of the weight loss achieved with semaglutide was regained.19 Thus, the weight-reducing effects of obesity medications seem to depend on continued usage. It is an unsolved challenge in the pharmacological treatment of obesity how medication can be terminated while minimising weight regain.

In contrast to pharmacotherapy, exercise is a low-cost intervention and represents a behavioural change that, in principle, can be continued in a real-world setting after termination of the supervised treatment. Most, but not all, studies on physical activity treatment programs have reported small, sustained increases in physical activity levels after termination of the supervised program.20, 21, 22, 23, 24 These studies are heterogeneous regarding duration, physical activity intervention, degree of supervision, and study population. It is, therefore, not established whether people who have completed a long-term exercise program remain more physically active in real-world settings after termination of the supervised program. In addition, it has not been investigated whether incorporating exercise together with GLP-1 receptor agonist treatment can improve the sustainability of healthy weight loss maintenance after treatment is terminated. If exercise combined with GLP-1 receptor agonist can limit weight regain after treatment termination, as compared with GLP-1 receptor agonist alone, it would emphasize that supervised exercise programs should be available and implemented for individuals seeking obesity pharmacotherapy.

Therefore, we investigated whether weight loss and improved body composition are sustained better at 1 year after termination of active treatment with GLP-1 receptor agonist, supervised exercise program, or both combined for 1 year. Specifically, we hypothesised that weight loss and body composition were preserved better one year after termination of supervised exercise combined with a GLP-1 receptor agonist as compared with the GLP-1 receptor agonist alone.

## Methods

### Study design

In this article, we report the results of a post-treatment study conducted in extension of a randomised, controlled trial.7 The study was conducted at the Department of Biomedical Sciences, University of Copenhagen, and the Department of Endocrinology, Copenhagen University Hospital—Hvidovre. The study protocol25 and primary trial report (including reported harms)7 have been published. The study CONSORT diagram is shown in Fig. 1.

#### Fig. 1.

[![Fig. 1](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c625/10965408/12b90e0ecb7a/gr1.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=10965408_gr1.jpg)

[Open in a new tab](figure/fig1/)

**Study CONSORT diagram**. Reasons for participants not attending the post-treatment study are shown. Reasons for participants not completing the low-calorie diet and 52-week intervention have been published previously.7

### Participants

Eligible participants were adults (aged 18–65 years) with obesity (body mass index 32–43 kg/m2). Serious chronic illnesses, including diabetes, were exclusion criteria. All eligibility criteria are available with the protocol.25 All participants who underwent randomisation were invited to participate in the post-treatment study regardless of completion of the active intervention.

### Randomisation and masking

Adults with obesity completed an eight-week low-calorie diet with at least 5% weight loss and were randomly allocated (1:1:1:1) to exercise plus placebo, liraglutide plus usual physical activity, combined exercise plus liraglutide, or placebo plus usual physical activity for 52 weeks.7 Randomisation was stratified by sex and age group (<40 years and ≥40 years of age). The participants, personnel, and investigators were blinded regarding study medication. Unblinding of the four intervention groups was performed after statistical analyses of body weight and body-fat percentage changes from randomisation to week 52. Participants remained blinded until they had attended the post-treatment study one year after treatment termination. The primary and secondary outcomes of the present study were analysed by a statistician blinded for group allocation.

### Procedures

The study design is shown in Fig. 2. Overall, the study consisted of three phases: an eight-week weight loss phase (week −8 to 0), a 52-week randomised, controlled weight maintenance phase (week 0–52), and a one-year post-treatment phase (week 52–104). The results of the first two phases, i.e., the weight loss (week −8 to 0) and weight maintenance (week 0–52) phases, have been published previously,7,26,27 and the results of this paper are based on the post-treatment phase alone (week 52–104) and in combination with the weight maintenance phase (week 0–104).

#### Fig. 2.

[![Fig. 2](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c625/10965408/ab7bb6b83d75/gr2.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=10965408_gr2.jpg)

[Open in a new tab](figure/fig2/)

**Study profile**. Participants who obtained a weight loss of at least 5% during an 8-week low-calorie diet were randomly allocated (1:1:1:1) to exercise plus placebo, once-daily subcutaneous liraglutide 3.0 mg plus usual physical activity, combined exercise plus liraglutide, or placebo plus usual physical activity for 52 weeks. All randomised participants were invited for post-treatment outcome assessments one year after treatment was stopped. In the one-year post-treatment phase, there was no contact between study participants and study personnel.

An initial weight loss before randomisation was chosen because the primary aim was to investigate maintenance of weight loss. To induce a similar, fast, and effective weight loss, all participants initially underwent a controlled low-calorie diet of 800 kcal/day for eight weeks, where all food was replaced with four meal replacement products per day (Cambridge Weight Plan). Participants who lost at least 5% of initial weight loss were then randomised.

Liraglutide or volume-matched placebo was administered once daily as subcutaneous injections. The starting dose was 0.6 mg per day with weekly increases of 0.6 mg until a tolerated dose of a maximum 3.0 mg per day was achieved. Liraglutide/placebo treatment was terminated after 52 weeks.

The exercise intervention started with a six-week introduction phase, where exercise volume was gradually increased. From week 7, participants were encouraged to attend supervised group exercise sessions twice per week and to exercise individually twice per week. Group exercise consisted of vigorous-intensity indoor cycling followed by circuit training. Exercise performed individually was of moderate-to-vigorous intensity, and the type of exercise was at the participants’ choice. All exercise was monitored with sports watches and heart rate monitors. Participants not allocated to exercise were encouraged to maintain habitual physical activity during the 52-week intervention period. At week 52, the supervised exercise program was terminated and participants returned the sports watches and heart rate monitors.

All participants who had undergone randomisation were invited to participate in the post-treatment study, which was composed of a set of outcome assessments one year after the planned completion of the 52-week weight maintenance intervention. To investigate the sustainability of the different weight maintenance treatments in a real-world setting, there was no contact between study participants and study personnel until the invitation to participate was sent by e-mail near completion of the second year. During the one-year post-treatment phase, none of the interventions were continued, and participants had neither restrictions nor encouragement in terms of weight management strategies. If the participants did not respond to the e-mail invitation, they were contacted by phone. Participants who agreed to attend, met in the morning at Hvidovre Hospital, Denmark, after having fasted for at least 10 h. The use of supplements, concomitant medication, and treatments for obesity (e.g., pharmacotherapy) were recorded.

Body weight, hip and waist circumferences, fasting glucose levels, blood pressure, and resting heart rate were measured in the fasted state before the low-calorie diet (week −8), at randomisation (week 0), at weeks 4, 13, 26, 39, 52 after randomisation, and one year after intervention completion (approximately 104 weeks after randomisation). Total body-fat and lean mass (dual-energy x-ray absorptiometry, Hologic Discovery), HbA1c, lipid levels, and self-reported quality of life were measured at weeks −8, 0, 52, and 104.

### Outcomes

The primary outcome of the study was the change in body weight (kg) from randomisation to one year after termination of the weight maintenance intervention (week 0–104). The change from randomisation to week 104 is a combination of the effects of one year on active treatment and one subsequent year off treatment. This outcome was chosen since both effects on treatment and off treatment are important to evaluate the sustainable benefits in a real-world setting. The key secondary outcome was the change in body-fat percentage (calculated as fat mass (kg) divided by body weight (kg) multiplied by 100) from week 0 to 104. Other outcomes related to metabolic health were changes from week 0 to 104 in fat mass, lean mass, waist and hip circumferences, HbA1c, fasting glucose, systolic and diastolic blood pressure, resting heart rate, and plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Changes in quality-of-life outcomes were assessed with a Danish version of the RAND 36-Item Short Form Health Survey,28 where scores in each domain range from 0 to 100, with higher scores indicating better health. Physical activity and sedentary time were objectively measured in the week leading up to the post-treatment study visit with wrist-worn accelerometers (GENEActiv, Activinsights Ltd.) analysed with the R-package GGIR v.2.9–029, 30, 31 and subjectively with the International Physical Activity Questionnaire.32

### Statistical analysis

Participants were initially recruited for the weight loss and weight loss maintenance phases of the study (week −8 to 52). To investigate the sustainability of the different weight loss maintenance treatments in a real-world situation, we invited all randomised participants to the post-treatment study (week 104). A statistical analysis plan was made before data was extracted and sent to the statistician for blinded analysis of primary and secondary outcomes (see Supplementary statistical analysis plan). Changes from randomisation to one year after treatment termination (week 0–104) in body weight (primary outcome) and body-fat percentage (secondary outcome) were tested in the intention-to-treat population (defined as all randomised participants irrespective of adherence and study completion) with multiple comparisons between all four groups for a total of 12 tests (6 for each outcome). To analyse changes in continuous outcomes over time, we applied a linear mixed model with time (categorical: week-8 = 1, week 0 = 2, week 4 = 3, week 13 = 4, week 26 = 5, week 39 = 6, week 52 = 7, and week 104 = 8), treatment group, a time–group interaction, sex, and age group (<40 years, ≥40 years) as fixed effects. To account for the correlation between repeated measurements, the model assumed an unstructured covariance pattern.33 None of the participants had missing data for any of the covariates. Missing data was implicitly handled by maximum likelihood estimation in the linear mixed model analyses. Categorical outcomes (weight loss ≥5%, ≥10%, ≥15%, and ≥20% from week −8 to 104) were analysed using logistic regression to investigate whether the probability of having sustained a weight loss one year after treatment termination was different between the four groups. The logistic regression analyses included group, sex, and age as factors. In the logistic regression analyses, for all participants who had missing body weight data at week 104, we used the predicted body weight value from the linear mixed model to calculate changes from week 0 to 104. These changes were used to categorise weight loss thresholds, and all randomised participants were therefore included in the analyses. The following supplementary analyses of primary and secondary outcomes were performed: a per-protocol analysis (excluding those who deviated from the protocol), an analysis with adjustment for the weight loss obtained during the initial low-calorie diet, a complete case analysis (excluding those who did not participate in the post-treatment study), and factor analyses testing (1) exercise groups combined (exercise and combination groups) versus no exercise groups combined (placebo and liraglutide groups) adjusted for the effect of liraglutide and (2) liraglutide groups combined (liraglutide and combination groups) versus placebo groups combined (placebo and exercise groups) adjusted for the effect of exercise. P values are provided for the primary analyses; P values < 0.05 with a false discovery rate <0.1 were considered statistically significant. The results of all other prespecified analyses are reported with point estimates and 95% confidence intervals unadjusted for multiple testing. All statistical analyses were performed in SAS Enterprise Guide version 8.1 (SAS Institute Inc.).

### Ethics

The study was approved by the Ethics Committee for the Capital Region of Denmark (H-16027082) and the Danish Medicines Agency and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice. The study is registered with EudraCT (2015-005585-32) and [ClinicalTrials.gov](http://ClinicalTrials.gov) ([NCT04122716](https://clinicaltrials.gov/ct2/show/NCT04122716)). Written informed consents were obtained for all participants before enrolment in the main study. Separate written informed consent was obtained for all participants who attended the post-treatment study.

### Role of the funding source

The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

## Results

Participants were recruited for the randomised controlled trial between Aug 29, 2016, and Sep 14, 2018.7 The post-treatment study was carried out from Dec 17, 2018, to Dec 17, 2020. A total of 109 participants attended the post-treatment study one year after planned intervention completion (Fig. 1), corresponding to 66% of those who completed the treatment phase. The mean time from treatment completion to post-treatment outcomes assessments was 55 ± 7 weeks. Characteristics of participants at randomisation were similar between the four intervention groups (Table S1) and similar between those who attended the post-treatment study and those who completed the active treatment but did not attend the post-treatment study (Table S2). Attendance was higher in the three groups who had received active treatment compared with placebo (Fig. 1). Four participants had initiated treatment with liraglutide in the post-treatment phase (one in the placebo group, one in the liraglutide group, and two in the exercise group).

Participants who had previously received liraglutide alone regained 9.6 kg in the one-year period after treatment was terminated (week 52–104), resulting in a net weight regain from randomisation (week 0–104) of 8.7 kg (Fig. 3A and B and Table S3). Participants who had received the combination of liraglutide and supervised exercise regained 7.1 kg in the off-treatment phase, resulting in a net weight change from randomisation (week 0–104) of 3.5 kg, which was 5.1 kg less than liraglutide alone (P = 0.040) and 4.1 kg less than placebo (P = 0.14). However, these changes did not meet the pre-specified false discovery rate (Table S4). Participants who had previously received supervised exercise alone regained 3.6 kg in the post-treatment phase. Thus, post-treatment weight regain was 6.0 kg (2.1–10.0) larger after liraglutide compared with after exercise and 2.5 kg (−1.5 to 6.5) compared with after combination treatment. The supplementary analyses of changes in body weight supported the primary analysis (Table S5). Those who attended the post-treatment study seemed to have a better response during the active treatment phase compared with those who completed the active treatment but did not attend the post-treatment study (Figure S1 and Table S6). The observed body weight measurements are shown in Fig. 3C, and the observed individual percentage weight changes from week −8 to week 104 are shown in Figure S2. More participants who had previously received combination treatment had a weight loss of at least 10% of initial body weight one year after treatment termination (week −8 to 104) compared with participants who had received placebo (odds ratio [OR] 7.2; 95% CI, 2.4; 21.3) and liraglutide (OR 4.2; 95% CI, 1.6; 10.8) (Fig. 3D and Table S7). More participants who had received exercise had a weight loss of at least 5% of initial body weight compared with liraglutide (OR 2.9; 95% CI, 1.3; 6.6) and at least 10% compared with placebo (OR 3.7, 95% CI, 1.2; 11.1). In the comparison of exercise versus non-exercise adjusted for the effect of liraglutide, exercise was associated with a weight reduction of −4.6 kg (−8.2 to −1.9) from week 0 to 104 (Fig. 3E). For liraglutide versus placebo adjusted for the effect of exercise, there was no weight reduction for liraglutide from week 0 to 104 (−0.7 kg; −4.3 to 2.9) (Fig. 3F).

### Fig. 3.

[![Fig. 3](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c625/10965408/b5656e56425b/gr3.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=10965408_gr3.jpg)

[Open in a new tab](figure/fig3/)

**Changes in body weight during the study**. Data are for the intention-to-treat population and reported as estimated mean ± SE changes derived from a linear mixed model with time, group, sex, age, and a time–group interaction as fixed effects unless otherwise stated. Panel A shows the estimated mean changes in body weight during a low-calorie diet (week −8 to 0), a weight maintenance intervention (week 0–52) with placebo, exercise plus placebo, liraglutide, or the combination of exercise and liraglutide, and a post-treatment phase (week 52–104). The randomisation value (week 0) is set to zero. Panel B shows the changes in body weight from randomisation (week 0) to week 104 with estimated mean differences and 95% confidence intervals between all four groups. Panel C shows the observed mean ± SE body weights in the study. Panel D shows a bar graph of the percentages of participants who had a weight loss at week 104 of at least 5%, 10%, 15%, and 20% of initial body weight (at week −8). Percentages were calculated using logistic regression. For missing data, categorisation was based on predicted values from the linear mixed model. Panel E shows the estimated mean changes in body weight from randomisation (week 0) for those who were randomised to exercise (exercise plus placebo and exercise plus liraglutide, n = 97) versus no exercise (placebo and liraglutide, n = 98) adjusted for the effect of liraglutide. Panel F shows the estimated mean changes in body weight from randomisation for those who were randomised to liraglutide (liraglutide and exercise plus liraglutide, n = 98) versus placebo (placebo and exercise plus placebo, n = 97) adjusted for the effect of exercise.

From randomisation to one year after treatment termination (week 0–104), participants who had previously received the combination treatment had a 2.3%-points decrease in fat percentage compared with participants who had previously received liraglutide (P = 0.026) (Fig. 4A and B), which did not meet the pre-specified false discovery rate (Table S4). The two exercise groups combined had reduced fat percentage compared with non-exercise groups (−1.5%-points; −3.0 to −0.0) (Fig. 4C) one year after treatment termination. In contrast, the two liraglutide groups combined had a similar fat percentage as placebo groups combined (0.0%-points; −1.5 to 1.5) (Fig. 4D).

### Fig. 4.

[![Fig. 4](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c625/10965408/632656803918/gr4.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=10965408_gr4.jpg)

[Open in a new tab](figure/fig4/)

**Changes in body composition during the study**. Data are for the intention-to-treat population and reported as estimated mean ± SE changes derived from a linear mixed model with time, group, sex, age, and a time–group interaction as fixed effects unless otherwise stated. Panel A shows the estimated mean changes in body-fat percentage during a low-calorie diet (week −8 to 0), a weight maintenance intervention (week 0–52) with placebo, exercise plus placebo, liraglutide, or the combination of exercise and liraglutide, and a post-treatment phase (week 52–104). The randomisation value (week 0) is set to zero. Panel B shows the changes in body-fat percentage from randomisation (week 0) to week 104 with estimated mean differences and 95% confidence intervals between all four groups. Panel C shows the estimated mean changes in body-fat percentage from randomisation for those who were randomised to exercise (exercise plus placebo and exercise plus liraglutide, n = 97) versus no exercise (placebo and liraglutide, n = 98) adjusted for the effect of liraglutide. Panel D shows the estimated mean changes in body-fat percentage from randomisation for those who were randomised to liraglutide (liraglutide and exercise plus liraglutide, n = 98) versus placebo (placebo and exercise plus placebo, n = 97) adjusted for the effect of exercise. Panel E shows the estimated mean changes in fat mass from randomisation. Panel F shows the estimated mean changes in waist circumference from randomisation.

The combination treatment resulted in decreased fat mass compared with liraglutide alone (Fig. 4E and Table S8) and decreased waist circumference compared with placebo and liraglutide alone (Fig. 4F). All groups had similar increases in lean mass (Figure S3).

Changes in outcomes related to metabolic health are shown in Figures S3 and S4 and Table S8. The improvements in HbA1c and fasting glucose that were obtained with liraglutide alone and combined with exercise were lost one year after treatment termination. The combination treatment was associated with reduced resting heart rate compared with liraglutide alone. Changes in outcomes from the RAND 36-Item Health Survey are shown in Figure S5 and Table S8. Participants who previously received the combination treatment had improved scores of physical functioning, less limitations due to physical health, and energy/fatigue compared with liraglutide alone. Exercise alone was associated with improved energy and fatigue and pain scores compared with liraglutide.

One year after treatment termination, participants who had received exercise alone or in combination with liraglutide reported the highest levels of moderate-to-vigorous-intensity physical activity. More people who had received liraglutide without exercise reported no activity: median 150 min/week for placebo, 240 min/week for exercise, 30 min/week for liraglutide, and 225 min/week for the combination treatment (Fig. 5A). Measures of physical activity with accelerometers also indicated higher levels of physical activity in the exercise groups (Fig. 5C). Self-reported sitting and accelerometer-measured sedentary time was similar between the groups (Fig. 5B and D).

### Fig. 5.

[![Fig. 5](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c625/10965408/78b9874876c7/gr5.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=10965408_gr5.jpg)

[Open in a new tab](figure/fig5/)

**Physical activity and sedentary time**. Violin plots of physical activity and sedentary time in the post-treatment study. Panel A shows the self-reported moderate-to-vigorous-intensity physical activity in the week leading up to post-treatment assessments (week 104). Panel B shows the self-reported daily sitting time in the week leading up to post-treatment assessments (week 104). Panel C shows the daily moderate-to-vigorous-intensity physical activity measured with accelerometers worn on the wrist in the week leading up to post-treatment assessments (week 104). Panel D shows the sedentary time measured from the accelerometers. The black lines indicate the medians, the white diamonds indicate the observed means, and the black dots indicate individual observations. Self-reported measures were calculated from the International Physical Activity Questionnaire.32 Accelerometer-derived measures were calculated with the R-package GGIR.29 _MVPA_ , moderate-to-vigorous-intensity physical activity.

## Discussion

In this study, we investigated whether exercise during obesity pharmacotherapy improved healthy weight maintenance after one year of active treatment followed by one year in a real-world setting after treatment was terminated. One year after treatment termination, participants who had previously received combined supervised exercise and GLP-1 receptor agonist treatment had maintained weight loss and body-fat reduction compared with GLP-1 receptor agonist alone. More participants who had previously received combination treatment maintained a weight loss of at least 10% of initial body weight one year after treatment termination compared with participants who had received liraglutide alone or placebo. Weight regain during the one-year post-treatment phase was 6 kg larger for participants who had previously received liraglutide alone compared with participants who had previously received supervised exercise alone, despite similar initial weight loss. Collectively, these results indicate that the addition of supervised exercise during obesity pharmacotherapy improves maintenance of healthy body weight and body composition after treatment termination.

In the intervention phase of the S-LiTE study, weight loss was successfully maintained for one year with exercise and liraglutide as separate treatments, and the combination of both was the most effective strategy in terms of healthy body weight and fat reduction.7 In the present study, approximately two-thirds of the initial weight loss had been regained one year after liraglutide treatment alone was stopped. This magnitude of regain with liraglutide alone is similar to that observed 52 weeks after a 68-week treatment phase with semaglutide 2.4 mg per week.19 However, clinical obesity trials with off-medication phases have not previously assessed fat mass.18,19,34,35 In our study, discontinuation of liraglutide alone was associated with a regain of 6.3 kg fat mass after one year, corresponding to a regain of more than 70% of the fat mass reduction after termination of liraglutide alone. In contrast, with liraglutide combined with exercise, after one year of habitual living after treatment termination, participants were 5.1 kg weight reduced compared with after termination of liraglutide alone. This difference resulted from a 2.7 kg larger weight reduction during active treatment and 2.5 kg less weight regain in the off-treatment period. The combination of liraglutide with exercise also led to lowered fat percentage, fat mass, and waist circumference compared with liraglutide alone, illustrating healthier body composition. A substantial larger proportion of participants who had exercised compared with non-exercise were able to sustain a weight loss of at least 10%, and greater, of initial body weight one year after treatment termination.

The analyses of exercise versus non-exercise groups showed that the improvements in body weight and body composition obtained with a one-year exercise intervention were maintained one year after the completion of the intervention. Conversely, the analyses contrasting liraglutide versus placebo groups showed that the benefits on body weight, body composition, and glucose levels obtained with liraglutide were lost one year after treatment. Therefore, our results show that supervised exercise, as a weight maintenance strategy, improves body weight and composition, which can be sustained after termination of the supervised exercise. In contrast, we found no indication of a sustained effect of liraglutide after the treatment had been terminated.

A possible explanation for the maintained benefits after exercise is that the participants remained more physically active on their own after the intervention. More participants who had exercised engaged in moderate- or vigorous-intensity physical activity in the week prior to the post-treatment assessments, compared to liraglutide alone, which was also confirmed in the questionnaires. Thus, people randomised to exercise may have had acquired exercise behaviours during the intervention and, therefore, were able to sustain higher physical activity levels after medication was stopped to minimise the otherwise insistent weight regain. This notion could also explain the observed improvements in resting heart rate and physical functioning after termination of combined exercise plus liraglutide compared with after termination of liraglutide alone. In the Finnish Diabetes Prevention Study, more participants in the lifestyle group than the control group remained physically active, as assessed by a self-reported questionnaire three years after the active intervention.24 In adults aged +65 years, exercise-based interventions led to sustained increases in physical activity six months after interventions, but not after one year.21 Thus, increases in physical activity may persist after controlled exercise interventions. Although the exercise program in our study was not specifically focused on maintaining habits after the intervention, a sustained effect on healthy weight was present one year after the intervention was completed. Despite the sustained weight and fat reduction after termination of combined exercise and liraglutide compared with after termination of liraglutide alone, some weight gain after treatment was not entirely prevented. Therefore, focused continued physical activity after the termination of pharmacotherapy is advisable for healthy weight maintenance. Future lifestyle-based treatments during obesity pharmacotherapy may further improve body weight and composition outcomes with an additional focus on strategies and tools to maintain healthy physical activity habits after termination of pharmacotherapy.

In our study, the weight regain resulting from one year of liraglutide treatment followed by one year off treatment exceeded the weight regain of the exercise and placebo treatments. GLP-1 receptor agonists induce weight loss primarily by appetite inhibition5,6,36 and slowed gastric emptying,37 and have been shown to improve eating behaviours, i.e., reduce uncontrolled and emotional eating and improve cognitive restraint.6,38 When GLP-1 receptor agoinst treatment is stopped, appetite inhibition and improved eating behaviours are lost, and the participants do not have any available means to counteract these changes, which is the likely cause for the observed rapid weight regain. This contrasts with physical activity interventions, where increased physical activity in principle can be continued in a real world-setting after intervention termination and, thus, treatments effects can be maintained.

The present study has several strengths. It is the first study to directly compare body weight changes after physical activity and obesity pharmaceutical interventions and investigate the combination of both. Body composition was assessed in addition to body weight using dual-energy X-ray absorptiometry to evaluate healthy weight. The inclusion of a one-year post-treatment phase with no active intervention reflects a real-world setting and is important in the evaluation of obesity treatments due to the relapsing nature of obesity. Weight regain often occurs after treatment termination, irrespective of whether the weight loss is obtained with medication or lifestyle-based interventions.19,39 Given the many people who initiate obesity pharmacotherapy worldwide but also terminate treatment again,14, 15, 16, 17 off-treatment assessments are imperative to elucidate the real-world potential of pharmacotherapy and are clinically relevant. Therefore, we investigated the sustainability of exercise-based and pharmacology-based single or combination treatment for weight loss maintenance in a real-world situation. A total of 71% of the participants who had completed an active weight maintenance treatment (exercise, liraglutide, or the combination) participated in the post-treatment study. The sample size in the active treatment groups was thus sufficiently high to give indications of what happens in a real-world situation. Overall, the loss to follow-up rates in our study were similar to other post-intervention follow-up studies of exercise and long-term pharmacological interventions.13,40,41

The study also has limitations. Fewer participants from the placebo group participated in the post-treatment study. It is common in obesity pharmacotherapy trials that more people in the placebo group are lost to follow-up than in the active treatment group.8,10,35 Here, we aimed to investigate and compare the sustainability of the different active weight loss maintenance treatments. For all treatment groups, those who attended the post-treatment study had a better mean treatment response during the active treatment than those who did not attend. However, in the statistical model, the repeated measurements recorded during the trial were used to estimate the missing values at the post-treatment assessment, thereby likely mitigating potential selection bias.

In summary, supervised exercise combined with obesity pharmacotherapy has the potential to prevent body weight and fat mass regain after treatment termination compared with obesity pharmacotherapy without exercise.

## Contributors

SST, SBKJ, and SM contributed to the design of the post-treatment study. SBKJ, LMO, RMS, CRJ, JRL, and CJ contributed to data collection of the S-LITE study. SBKJ and LMO contributed to the practical conduction of the post-treatment study. SST, SBKJ, and MBB wrote the statistical analysis plan with contributions from CRJ, SM, BMS, and JJH. MBB performed the analyses of primary and secondary outcomes, and SBKJ performed the analyses of supportive outcomes. SBKJ and RMS processed accelerometer data. SBKJ and SST wrote the first draft of the manuscript. All authors contributed to subsequent drafts and interpretation of data. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

## Data sharing statement

De-identified participant data that underlie the results reported in this article will be made available for research collaboration purposes upon request and approval of the requested use of data by the corresponding author and will require the completion of a data processing agreement.

## Declaration of interests

RMS: family member owns Novo Nordisk stocks.

S.M.: _Advisory boards:_ AstraZeneca; Boehringer Ingelheim; Eli Lilly; Merck Sharp & Dohme; Novo Nordisk; Sanofi Aventis. _Lecture fees:_ AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi Aventis. _Research Grant Recipient_ : Novo Nordisk, Boehringer-Ingelheim.

S.S.T.: _Research Grant and Lecture Fee Recipient_ : Novo Nordisk.

J.J.H.: _Advisory board:_ Novo Nordisk.

M.B.B.: _Research Grant_ Novo Nordisk A/S, payment made to institution.

B.M.S.: Board member of Steno Diabetes Center Copenhagen. Board member of the Centre for Childhood Health, appointed by the Novo Nordisk Foundation.

## Acknowledgements

The study was funded by the Novo Nordisk Foundation (NNF16OC0019968 and NNF15CC0018486) and Helsefonden (20-B-0389). The authors thank all who agreed to participate in the study. Novo Nordisk A/S supplied study medication (liraglutide and placebo pens). Cambridge Weight Plan supplied meal replacement products for the low-calorie diet.

## Footnotes

Appendix A

Supplementary data related to this article can be found at <https://doi.org/10.1016/j.eclinm.2024.102475>.

## Appendix A. Supplementary data

Figure S1–S5 and Table S1–S8

[mmc1.docx](/articles/instance/10965408/bin/mmc1.docx) (1.2MB, docx) 

Statistical Analysis

[mmc2.pdf](/articles/instance/10965408/bin/mmc2.pdf) (1.2MB, pdf) 

## References

  * 1.Avila C., Holloway A.C., Hahn M.K., et al. An overview of links between obesity and mental health. Curr Obes Rep. 2015;4(3):303–310. doi: 10.1007/s13679-015-0164-9. [[DOI](https://doi.org/10.1007/s13679-015-0164-9)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/26627487/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Curr%20Obes%20Rep&title=An%20overview%20of%20links%20between%20obesity%20and%20mental%20health&author=C.%20Avila&author=A.C.%20Holloway&author=M.K.%20Hahn&volume=4&issue=3&publication_year=2015&pages=303-310&pmid=26627487&doi=10.1007/s13679-015-0164-9&)]
  * 2.Kolotkin R.L., Andersen J.R. A systematic review of reviews: exploring the relationship between obesity, weight loss and health-related quality of life. Clin Obes. 2017;7(5):273–289. doi: 10.1111/cob.12203. [[DOI](https://doi.org/10.1111/cob.12203)] [[PMC free article](/articles/PMC5600094/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/28695722/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Clin%20Obes&title=A%20systematic%20review%20of%20reviews:%20exploring%20the%20relationship%20between%20obesity,%20weight%20loss%20and%20health-related%20quality%20of%20life&author=R.L.%20Kolotkin&author=J.R.%20Andersen&volume=7&issue=5&publication_year=2017&pages=273-289&pmid=28695722&doi=10.1111/cob.12203&)]
  * 3.Powell-Wiley T.M., Poirier P., Burke L.E., et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2021;143(21):E984–E1010. doi: 10.1161/CIR.0000000000000973. [[DOI](https://doi.org/10.1161/CIR.0000000000000973)] [[PMC free article](/articles/PMC8493650/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33882682/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Circulation&title=Obesity%20and%20cardiovascular%20disease:%20a%20scientific%20statement%20from%20the%20American%20Heart%20Association&author=T.M.%20Powell-Wiley&author=P.%20Poirier&author=L.E.%20Burke&volume=143&issue=21&publication_year=2021&pages=E984-E1010&pmid=33882682&doi=10.1161/CIR.0000000000000973&)]
  * 4.Narayan K.M.V., Boyle J.P., Thompson T.J., Gregg E.W., Williamson D.F. Effect of BMI on lifetime risk for diabetes in the U.S. Diabetes Care. 2007;30(6):1562–1566. doi: 10.2337/dc06-2544. [[DOI](https://doi.org/10.2337/dc06-2544)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17372155/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Diabetes%20Care&title=Effect%20of%20BMI%20on%20lifetime%20risk%20for%20diabetes%20in%20the%20U.S&author=K.M.V.%20Narayan&author=J.P.%20Boyle&author=T.J.%20Thompson&author=E.W.%20Gregg&author=D.F.%20Williamson&volume=30&issue=6&publication_year=2007&pages=1562-1566&pmid=17372155&doi=10.2337/dc06-2544&)]
  * 5.Friedrichsen M., Breitschaft A., Tadayon S., Wizert A., Skovgaard D. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes Obes Metab. 2021;23(3):754–762. doi: 10.1111/dom.14280. [[DOI](https://doi.org/10.1111/dom.14280)] [[PMC free article](/articles/PMC7898914/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33269530/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Diabetes%20Obes%20Metab&title=The%20effect%20of%20semaglutide%202.4%20mg%20once%20weekly%20on%20energy%20intake,%20appetite,%20control%20of%20eating,%20and%20gastric%20emptying%20in%20adults%20with%20obesity&author=M.%20Friedrichsen&author=A.%20Breitschaft&author=S.%20Tadayon&author=A.%20Wizert&author=D.%20Skovgaard&volume=23&issue=3&publication_year=2021&pages=754-762&pmid=33269530&doi=10.1111/dom.14280&)]
  * 6.Jensen S.B.K., Janus C., Lundgren J.R., et al. Exploratory analysis of eating- and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment. Nat Commun. 2022;13(1):4770. doi: 10.1038/s41467-022-32307-y. [[DOI](https://doi.org/10.1038/s41467-022-32307-y)] [[PMC free article](/articles/PMC9378667/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/35970829/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Nat%20Commun&title=Exploratory%20analysis%20of%20eating-%20and%20physical%20activity-related%20outcomes%20from%20a%20randomized%20controlled%20trial%20for%20weight%20loss%20maintenance%20with%20exercise%20and%20liraglutide%20single%20or%20combination%20treatment&author=S.B.K.%20Jensen&author=C.%20Janus&author=J.R.%20Lundgren&volume=13&issue=1&publication_year=2022&pages=4770&pmid=35970829&doi=10.1038/s41467-022-32307-y&)]
  * 7.Lundgren J.R., Janus C., Jensen S.B.K., et al. Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med. 2021;384(18):1719–1730. doi: 10.1056/NEJMoa2028198. [[DOI](https://doi.org/10.1056/NEJMoa2028198)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33951361/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Healthy%20weight%20loss%20maintenance%20with%20exercise,%20liraglutide,%20or%20both%20combined&author=J.R.%20Lundgren&author=C.%20Janus&author=S.B.K.%20Jensen&volume=384&issue=18&publication_year=2021&pages=1719-1730&pmid=33951361&doi=10.1056/NEJMoa2028198&)]
  * 8.Wilding J.P.H., Batterham R.L., Calanna S., et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002. doi: 10.1056/NEJMoa2032183. [[DOI](https://doi.org/10.1056/NEJMoa2032183)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33567185/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Once-weekly%20semaglutide%20in%20adults%20with%20overweight%20or%20obesity&author=J.P.H.%20Wilding&author=R.L.%20Batterham&author=S.%20Calanna&volume=384&issue=11&publication_year=2021&pages=989-1002&pmid=33567185&doi=10.1056/NEJMoa2032183&)]
  * 9.Jastreboff A.M., Aronne L.J., Ahmad N.N., et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205–216. doi: 10.1056/NEJMoa2206038. [[DOI](https://doi.org/10.1056/NEJMoa2206038)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/35658024/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Tirzepatide%20once%20weekly%20for%20the%20treatment%20of%20obesity&author=A.M.%20Jastreboff&author=L.J.%20Aronne&author=N.N.%20Ahmad&volume=387&issue=3&publication_year=2022&pages=205-216&pmid=35658024&doi=10.1056/NEJMoa2206038&)]
  * 10.Pi-Sunyer X., Astrup A., Fujioka K., et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373(1):11–22. doi: 10.1056/NEJMoa1411892. [[DOI](https://doi.org/10.1056/NEJMoa1411892)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/26132939/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=A%20randomized,%20controlled%20trial%20of%203.0%20mg%20of%20liraglutide%20in%20weight%20management&author=X.%20Pi-Sunyer&author=A.%20Astrup&author=K.%20Fujioka&volume=373&issue=1&publication_year=2015&pages=11-22&pmid=26132939&doi=10.1056/NEJMoa1411892&)]
  * 11.Rubino D.M., Greenway F.L., Khalid U., et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022;327(2):138. doi: 10.1001/jama.2021.23619. [[DOI](https://doi.org/10.1001/jama.2021.23619)] [[PMC free article](/articles/PMC8753508/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/35015037/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=JAMA&title=Effect%20of%20weekly%20subcutaneous%20semaglutide%20vs%20daily%20liraglutide%20on%20body%20weight%20in%20adults%20with%20overweight%20or%20obesity%20without%20diabetes:%20the%20STEP%208%20randomized%20clinical%20trial&author=D.M.%20Rubino&author=F.L.%20Greenway&author=U.%20Khalid&volume=327&issue=2&publication_year=2022&pages=138&pmid=35015037&doi=10.1001/jama.2021.23619&)]
  * 12.Marso S.P., Daniels G.H., Brown-Frandsen K., et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–322. doi: 10.1056/NEJMoa1603827. [[DOI](https://doi.org/10.1056/NEJMoa1603827)] [[PMC free article](/articles/PMC4985288/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/27295427/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Liraglutide%20and%20cardiovascular%20outcomes%20in%20type%202%20diabetes&author=S.P.%20Marso&author=G.H.%20Daniels&author=K.%20Brown-Frandsen&volume=375&issue=4&publication_year=2016&pages=311-322&pmid=27295427&doi=10.1056/NEJMoa1603827&)]
  * 13.Le Roux C.W., Astrup A., Fujioka K., et al. 3 Years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. 2017;389(10077):1399–1409. doi: 10.1016/S0140-6736(17)30069-7. [[DOI](https://doi.org/10.1016/S0140-6736\(17\)30069-7)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/28237263/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Lancet&title=3%20Years%20of%20liraglutide%20versus%20placebo%20for%20type%202%20diabetes%20risk%20reduction%20and%20weight%20management%20in%20individuals%20with%20prediabetes:%20a%20randomised,%20double-blind%20trial&author=C.W.%20Le%20Roux&author=A.%20Astrup&author=K.%20Fujioka&volume=389&issue=10077&publication_year=2017&pages=1399-1409&pmid=28237263&doi=10.1016/S0140-6736\(17\)30069-7&)]
  * 14.Wharton S., Haase C.L., Kamran E., et al. Weight loss and persistence with liraglutide 3.0 mg by obesity class in the real-world effectiveness study in Canada. Obes Sci Pract. 2020;6(4):439. doi: 10.1002/osp4.420. [[DOI](https://doi.org/10.1002/osp4.420)] [[PMC free article](/articles/PMC7448201/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/32874678/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Obes%20Sci%20Pract&title=Weight%20loss%20and%20persistence%20with%20liraglutide%203.0%20mg%20by%20obesity%20class%20in%20the%20real-world%20effectiveness%20study%20in%20Canada&author=S.%20Wharton&author=C.L.%20Haase&author=E.%20Kamran&volume=6&issue=4&publication_year=2020&pages=439&pmid=32874678&doi=10.1002/osp4.420&)]
  * 15.Ganguly R., Tian Y., Kong S.X., et al. Persistence of newer anti-obesity medications in a real-world setting. Diabetes Res Clin Pract. 2018;143:348–356. doi: 10.1016/j.diabres.2018.07.017. [[DOI](https://doi.org/10.1016/j.diabres.2018.07.017)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/30009937/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Diabetes%20Res%20Clin%20Pract&title=Persistence%20of%20newer%20anti-obesity%20medications%20in%20a%20real-world%20setting&author=R.%20Ganguly&author=Y.%20Tian&author=S.X.%20Kong&volume=143&publication_year=2018&pages=348-356&pmid=30009937&doi=10.1016/j.diabres.2018.07.017&)]
  * 16.Weiss T., Carr R.D., Pal S., et al. Real-world adherence and discontinuation of glucagon-like peptide-1 receptor agonists therapy in type 2 diabetes mellitus patients in the United States. Patient Prefer Adherence. 2020;14:2337. doi: 10.2147/PPA.S277676. [[DOI](https://doi.org/10.2147/PPA.S277676)] [[PMC free article](/articles/PMC7708309/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33273810/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Patient%20Prefer%20Adherence&title=Real-world%20adherence%20and%20discontinuation%20of%20glucagon-like%20peptide-1%20receptor%20agonists%20therapy%20in%20type%202%20diabetes%20mellitus%20patients%20in%20the%20United%20States&author=T.%20Weiss&author=R.D.%20Carr&author=S.%20Pal&volume=14&publication_year=2020&pages=2337&pmid=33273810&doi=10.2147/PPA.S277676&)]
  * 17.Weiss T., Yang L., Carr R.D., et al. Real-world weight change, adherence, and discontinuation among patients with type 2 diabetes initiating glucagon-like peptide-1 receptor agonists in the UK. BMJ Open Diabetes Res Care. 2022;10(1):e002517. doi: 10.1136/bmjdrc-2021-002517. [[DOI](https://doi.org/10.1136/bmjdrc-2021-002517)] [[PMC free article](/articles/PMC8804648/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/35101924/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BMJ%20Open%20Diabetes%20Res%20Care&title=Real-world%20weight%20change,%20adherence,%20and%20discontinuation%20among%20patients%20with%20type%202%20diabetes%20initiating%20glucagon-like%20peptide-1%20receptor%20agonists%20in%20the%20UK&author=T.%20Weiss&author=L.%20Yang&author=R.D.%20Carr&volume=10&issue=1&publication_year=2022&pages=e002517&pmid=35101924&doi=10.1136/bmjdrc-2021-002517&)]
  * 18.Rubino D., Abrahamsson N., Davies M., et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. J Am Med Assoc. 2021;325(14):1414–1425. doi: 10.1001/jama.2021.3224. [[DOI](https://doi.org/10.1001/jama.2021.3224)] [[PMC free article](/articles/PMC7988425/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33755728/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Am%20Med%20Assoc&title=Effect%20of%20continued%20weekly%20subcutaneous%20semaglutide%20vs%20placebo%20on%20weight%20loss%20maintenance%20in%20adults%20with%20overweight%20or%20obesity:%20the%20STEP%204%20randomized%20clinical%20trial&author=D.%20Rubino&author=N.%20Abrahamsson&author=M.%20Davies&volume=325&issue=14&publication_year=2021&pages=1414-1425&pmid=33755728&doi=10.1001/jama.2021.3224&)]
  * 19.Wilding J.P.H., Batterham R.L., Davies M., et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553–1564. doi: 10.1111/dom.14725. [[DOI](https://doi.org/10.1111/dom.14725)] [[PMC free article](/articles/PMC9542252/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/35441470/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Diabetes%20Obes%20Metab&title=Weight%20regain%20and%20cardiometabolic%20effects%20after%20withdrawal%20of%20semaglutide:%20the%20STEP%201%20trial%20extension&author=J.P.H.%20Wilding&author=R.L.%20Batterham&author=M.%20Davies&volume=24&issue=8&publication_year=2022&pages=1553-1564&pmid=35441470&doi=10.1111/dom.14725&)]
  * 20.Andersen E., Burton N.W., Anderssen S.A. Physical activity levels six months after a randomised controlled physical activity intervention for Pakistani immigrant men living in Norway. Int J Behav Nutr Phys Activ. 2012;9(1):47. doi: 10.1186/1479-5868-9-47. [[DOI](https://doi.org/10.1186/1479-5868-9-47)] [[PMC free article](/articles/PMC3419654/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22537281/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Behav%20Nutr%20Phys%20Activ&title=Physical%20activity%20levels%20six%20months%20after%20a%20randomised%20controlled%20physical%20activity%20intervention%20for%20Pakistani%20immigrant%20men%20living%20in%20Norway&author=E.%20Andersen&author=N.W.%20Burton&author=S.A.%20Anderssen&volume=9&issue=1&publication_year=2012&pages=47&pmid=22537281&doi=10.1186/1479-5868-9-47&)]
  * 21.Sansano-Nadal O., Giné-Garriga M., Brach J.S., et al. Exercise-based interventions to enhance long-term sustainability of physical activity in older adults: a systematic review and meta-analysis of randomized clinical trials. Int J Environ Res Public Health. 2019;16(14):2527. doi: 10.3390/ijerph16142527. [[DOI](https://doi.org/10.3390/ijerph16142527)] [[PMC free article](/articles/PMC6678490/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/31311165/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Environ%20Res%20Public%20Health&title=Exercise-based%20interventions%20to%20enhance%20long-term%20sustainability%20of%20physical%20activity%20in%20older%20adults:%20a%20systematic%20review%20and%20meta-analysis%20of%20randomized%20clinical%20trials&author=O.%20Sansano-Nadal&author=M.%20Gin%C3%A9-Garriga&author=J.S.%20Brach&volume=16&issue=14&publication_year=2019&pages=2527&pmid=31311165&doi=10.3390/ijerph16142527&)]
  * 22.Skogstad M., Lunde L.K., Ulvestad B., et al. The effect of a leisure time physical activity intervention delivered via a workplace: 15-month follow-up study. Int J Environ Res Public Health. 2018;15(2):1–13. doi: 10.3390/ijerph15020264. [[DOI](https://doi.org/10.3390/ijerph15020264)] [[PMC free article](/articles/PMC5858333/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/29401699/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Environ%20Res%20Public%20Health&title=The%20effect%20of%20a%20leisure%20time%20physical%20activity%20intervention%20delivered%20via%20a%20workplace:%2015-month%20follow-up%20study&author=M.%20Skogstad&author=L.K.%20Lunde&author=B.%20Ulvestad&volume=15&issue=2&publication_year=2018&pages=1-13&pmid=29401699&doi=10.3390/ijerph15020264&)]
  * 23.Henderson R.M., Miller M.E., Fielding R.A., et al. Maintenance of physical function 1 Year after exercise intervention in at-risk older adults: follow-up from the LIFE study. J Gerontol A Biol Sci Med Sci. 2018;73(5):688–694. doi: 10.1093/gerona/glx231. [[DOI](https://doi.org/10.1093/gerona/glx231)] [[PMC free article](/articles/PMC5905630/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/29490012/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Gerontol%20A%20Biol%20Sci%20Med%20Sci&title=Maintenance%20of%20physical%20function%201%20Year%20after%20exercise%20intervention%20in%20at-risk%20older%20adults:%20follow-up%20from%20the%20LIFE%20study&author=R.M.%20Henderson&author=M.E.%20Miller&author=R.A.%20Fielding&volume=73&issue=5&publication_year=2018&pages=688-694&pmid=29490012&doi=10.1093/gerona/glx231&)]
  * 24.Lindström J., Ilanne-Parikka P., Peltonen M., et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006;368(9548):1673–1679. doi: 10.1016/S0140-6736(06)69701-8. [[DOI](https://doi.org/10.1016/S0140-6736\(06\)69701-8)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17098085/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Lancet&title=Sustained%20reduction%20in%20the%20incidence%20of%20type%202%20diabetes%20by%20lifestyle%20intervention:%20follow-up%20of%20the%20Finnish%20Diabetes%20Prevention%20Study&author=J.%20Lindstr%C3%B6m&author=P.%20Ilanne-Parikka&author=M.%20Peltonen&volume=368&issue=9548&publication_year=2006&pages=1673-1679&pmid=17098085&doi=10.1016/S0140-6736\(06\)69701-8&)]
  * 25.Jensen S.B.K., Lundgren J.R., Janus C., et al. Protocol for a randomised controlled trial of the combined effects of the GLP-1 receptor agonist liraglutide and exercise on maintenance of weight loss and health after a very low-calorie diet. BMJ Open. 2019;9(11):e031431. doi: 10.1136/bmjopen-2019-031431. [[DOI](https://doi.org/10.1136/bmjopen-2019-031431)] [[PMC free article](/articles/PMC6830609/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/31678947/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BMJ%20Open&title=Protocol%20for%20a%20randomised%20controlled%20trial%20of%20the%20combined%20effects%20of%20the%20GLP-1%20receptor%20agonist%20liraglutide%20and%20exercise%20on%20maintenance%20of%20weight%20loss%20and%20health%20after%20a%20very%20low-calorie%20diet&author=S.B.K.%20Jensen&author=J.R.%20Lundgren&author=C.%20Janus&volume=9&issue=11&publication_year=2019&pages=e031431&pmid=31678947&doi=10.1136/bmjopen-2019-031431&)]
  * 26.Jensen S.B.K., Juhl C.R., Janus C., et al. Weight-loss maintenance with exercise and liraglutide improves glucose tolerance, glucagon response, and beta cell function. Obesity. 2023;31(4):977–989. doi: 10.1002/oby.23715. [[DOI](https://doi.org/10.1002/oby.23715)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/36942420/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Obesity&title=Weight-loss%20maintenance%20with%20exercise%20and%20liraglutide%20improves%20glucose%20tolerance,%20glucagon%20response,%20and%20beta%20cell%20function&author=S.B.K.%20Jensen&author=C.R.%20Juhl&author=C.%20Janus&volume=31&issue=4&publication_year=2023&pages=977-989&pmid=36942420&doi=10.1002/oby.23715&)]
  * 27.Sandsdal R.M., Juhl C.R., Jensen S.B.K., et al. Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial. Cardiovasc Diabetol. 2023;22(1):41. doi: 10.1186/s12933-023-01765-z. [[DOI](https://doi.org/10.1186/s12933-023-01765-z)] [[PMC free article](/articles/PMC9960425/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/36841762/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cardiovasc%20Diabetol&title=Combination%20of%20exercise%20and%20GLP-1%20receptor%20agonist%20treatment%20reduces%20severity%20of%20metabolic%20syndrome,%20abdominal%20obesity,%20and%20inflammation:%20a%20randomized%20controlled%20trial&author=R.M.%20Sandsdal&author=C.R.%20Juhl&author=S.B.K.%20Jensen&volume=22&issue=1&publication_year=2023&pages=41&pmid=36841762&doi=10.1186/s12933-023-01765-z&)]
  * 28.Hays R.D., Sherbourne C.D., Mazel R.M. The rand 36-item health survey 1.0. Health Econ. 1993;2(3):217–227. doi: 10.1002/hec.4730020305. [[DOI](https://doi.org/10.1002/hec.4730020305)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8275167/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Health%20Econ&title=The%20rand%2036-item%20health%20survey%201.0&author=R.D.%20Hays&author=C.D.%20Sherbourne&author=R.M.%20Mazel&volume=2&issue=3&publication_year=1993&pages=217-227&pmid=8275167&doi=10.1002/hec.4730020305&)]
  * 29.Migueles J.H., Rowlands A.V., Huber F., Sabia S., van Hees V.T. GGIR: a research community–driven open source R package for generating physical activity and sleep outcomes from multi-day raw accelerometer data. J Meas Phys Behav. 2019;2(3):188–196. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Meas%20Phys%20Behav&title=GGIR:%20a%20research%20community%E2%80%93driven%20open%20source%20R%20package%20for%20generating%20physical%20activity%20and%20sleep%20outcomes%20from%20multi-day%20raw%20accelerometer%20data&author=J.H.%20Migueles&author=A.V.%20Rowlands&author=F.%20Huber&author=S.%20Sabia&author=V.T.%20van%20Hees&volume=2&issue=3&publication_year=2019&pages=188-196&)]
  * 30.van Hees V.T., Gorzelniak L., Dean León E.C., et al. Separating movement and gravity components in an acceleration signal and implications for the assessment of human daily physical activity. PLoS One. 2013;8(4) doi: 10.1371/journal.pone.0061691. [[DOI](https://doi.org/10.1371/journal.pone.0061691)] [[PMC free article](/articles/PMC3634007/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/23626718/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=PLoS%20One&title=Separating%20movement%20and%20gravity%20components%20in%20an%20acceleration%20signal%20and%20implications%20for%20the%20assessment%20of%20human%20daily%20physical%20activity&author=V.T.%20van%20Hees&author=L.%20Gorzelniak&author=E.C.%20Dean%20Le%C3%B3n&volume=8&issue=4&publication_year=2013&pmid=23626718&doi=10.1371/journal.pone.0061691&)]
  * 31.Van Hees V.T., Fang Z., Langford J., et al. Autocalibration of accelerometer data for free-living physical activity assessment using local gravity and temperature: an evaluation on four continents. J Appl Physiol. 2014;117(7):738–744. doi: 10.1152/japplphysiol.00421.2014. [[DOI](https://doi.org/10.1152/japplphysiol.00421.2014)] [[PMC free article](/articles/PMC4187052/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/25103964/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Appl%20Physiol&title=Autocalibration%20of%20accelerometer%20data%20for%20free-living%20physical%20activity%20assessment%20using%20local%20gravity%20and%20temperature:%20an%20evaluation%20on%20four%20continents&author=V.T.%20Van%20Hees&author=Z.%20Fang&author=J.%20Langford&volume=117&issue=7&publication_year=2014&pages=738-744&pmid=25103964&doi=10.1152/japplphysiol.00421.2014&)]
  * 32.Booth M. Assessment of physical activity: an international perspective. Res Q Sport Exerc. 2000;71(Sup 2):114–120. doi: 10.1080/02701367.2000.11082794. [[DOI](https://doi.org/10.1080/02701367.2000.11082794)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/25680021/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Res%20Q%20Sport%20Exerc&title=Assessment%20of%20physical%20activity:%20an%20international%20perspective&author=M.%20Booth&volume=71&issue=Sup%202&publication_year=2000&pages=114-120&pmid=25680021&doi=10.1080/02701367.2000.11082794&)]
  * 33.Fitzmaurice G., Laird N., Ware J. John Wiley & Sons 2012; 2012. Applied longitudinal analysis. [[Google Scholar](https://scholar.google.com/scholar_lookup?Fitzmaurice%20G.,%20Laird%20N.,%20Ware%20J.%20John%20Wiley%20&%20Sons%202012;%202012.%20Applied%20longitudinal%20analysis.)]
  * 34.James W.P.T., Astrup A., Finer N., et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet. 2000;356(9248):2119–2125. doi: 10.1016/s0140-6736(00)03491-7. [[DOI](https://doi.org/10.1016/s0140-6736\(00\)03491-7)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11191537/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Lancet&title=Effect%20of%20sibutramine%20on%20weight%20maintenance%20after%20weight%20loss:%20a%20randomised%20trial&author=W.P.T.%20James&author=A.%20Astrup&author=N.%20Finer&volume=356&issue=9248&publication_year=2000&pages=2119-2125&pmid=11191537&doi=10.1016/s0140-6736\(00\)03491-7&)]
  * 35.Smith S.R., Weissman N.J., Anderson C.M., et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245–256. doi: 10.1056/NEJMoa0909809. [[DOI](https://doi.org/10.1056/NEJMoa0909809)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/20647200/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Multicenter,%20placebo-controlled%20trial%20of%20lorcaserin%20for%20weight%20management&author=S.R.%20Smith&author=N.J.%20Weissman&author=C.M.%20Anderson&volume=363&issue=3&publication_year=2010&pages=245-256&pmid=20647200&doi=10.1056/NEJMoa0909809&)]
  * 36.Blundell J., Finlayson G., Axelsen M., et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017;19(9):1242–1251. doi: 10.1111/dom.12932. [[DOI](https://doi.org/10.1111/dom.12932)] [[PMC free article](/articles/PMC5573908/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/28266779/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Diabetes%20Obes%20Metab&title=Effects%20of%20once-weekly%20semaglutide%20on%20appetite,%20energy%20intake,%20control%20of%20eating,%20food%20preference%20and%20body%20weight%20in%20subjects%20with%20obesity&author=J.%20Blundell&author=G.%20Finlayson&author=M.%20Axelsen&volume=19&issue=9&publication_year=2017&pages=1242-1251&pmid=28266779&doi=10.1111/dom.12932&)]
  * 37.Maselli D., Atieh J., Clark M.M., et al. Effects of liraglutide on gastrointestinal functions and weight in obesity: a randomized clinical and pharmacogenomic trial. Obesity. 2022;30(8):1608–1620. doi: 10.1002/oby.23481. [[DOI](https://doi.org/10.1002/oby.23481)] [[PMC free article](/articles/PMC9335902/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/35894080/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Obesity&title=Effects%20of%20liraglutide%20on%20gastrointestinal%20functions%20and%20weight%20in%20obesity:%20a%20randomized%20clinical%20and%20pharmacogenomic%20trial&author=D.%20Maselli&author=J.%20Atieh&author=M.M.%20Clark&volume=30&issue=8&publication_year=2022&pages=1608-1620&pmid=35894080&doi=10.1002/oby.23481&)]
  * 38.Nicolau J., Pujol A., Tofé S., Bonet A., Gil A. Short term effects of semaglutide on emotional eating and other abnormal eating patterns among subjects living with obesity. Physiol Behav. 2022;257 doi: 10.1016/J.PHYSBEH.2022.113967. [[DOI](https://doi.org/10.1016/J.PHYSBEH.2022.113967)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/36162525/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Physiol%20Behav&title=Short%20term%20effects%20of%20semaglutide%20on%20emotional%20eating%20and%20other%20abnormal%20eating%20patterns%20among%20subjects%20living%20with%20obesity&author=J.%20Nicolau&author=A.%20Pujol&author=S.%20Tof%C3%A9&author=A.%20Bonet&author=A.%20Gil&volume=257&publication_year=2022&pmid=36162525&doi=10.1016/J.PHYSBEH.2022.113967&)]
  * 39.Barte J.C.M., Ter Bogt N.C.W., Bogers R.P., et al. Maintenance of weight loss after lifestyle interventions for overweight and obesity, a systematic review. Obes Rev. 2010;11(12):899–906. doi: 10.1111/j.1467-789X.2010.00740.x. [[DOI](https://doi.org/10.1111/j.1467-789X.2010.00740.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/20345430/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Obes%20Rev&title=Maintenance%20of%20weight%20loss%20after%20lifestyle%20interventions%20for%20overweight%20and%20obesity,%20a%20systematic%20review&author=J.C.M.%20Barte&author=N.C.W.%20Ter%20Bogt&author=R.P.%20Bogers&volume=11&issue=12&publication_year=2010&pages=899-906&pmid=20345430&doi=10.1111/j.1467-789X.2010.00740.x&)]
  * 40.Quist J.S., Winther J., Friis A.L., et al. Maintenance of cardiorespiratory fitness, body composition, and a physically active lifestyle after structured exercise interventions in individuals with overweight and obesity: a mixed-method follow-up study. Public Health Pract. 2022;4 doi: 10.1016/j.puhip.2022.100293. [[DOI](https://doi.org/10.1016/j.puhip.2022.100293)] [[PMC free article](/articles/PMC9773044/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/36570402/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Public%20Health%20Pract&title=Maintenance%20of%20cardiorespiratory%20fitness,%20body%20composition,%20and%20a%20physically%20active%20lifestyle%20after%20structured%20exercise%20interventions%20in%20individuals%20with%20overweight%20and%20obesity:%20a%20mixed-method%20follow-up%20study&author=J.S.%20Quist&author=J.%20Winther&author=A.L.%20Friis&volume=4&publication_year=2022&pmid=36570402&doi=10.1016/j.puhip.2022.100293&)]
  * 41.Murray J.M., Brennan S.F., French D.P., Patterson C.C., Kee F., Hunter R.F. Effectiveness of physical activity interventions in achieving behaviour change maintenance in young and middle aged adults: a systematic review and meta-analysis. Soc Sci Med. 2017;192:125–133. doi: 10.1016/j.socscimed.2017.09.021. [[DOI](https://doi.org/10.1016/j.socscimed.2017.09.021)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/28965003/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Soc%20Sci%20Med&title=Effectiveness%20of%20physical%20activity%20interventions%20in%20achieving%20behaviour%20change%20maintenance%20in%20young%20and%20middle%20aged%20adults:%20a%20systematic%20review%20and%20meta-analysis&author=J.M.%20Murray&author=S.F.%20Brennan&author=D.P.%20French&author=C.C.%20Patterson&author=F.%20Kee&volume=192&publication_year=2017&pages=125-133&pmid=28965003&doi=10.1016/j.socscimed.2017.09.021&)]



## Associated Data

_This section collects any data citations, data availability statements, or supplementary materials included in this article._

### Supplementary Materials

Figure S1–S5 and Table S1–S8

[mmc1.docx](/articles/instance/10965408/bin/mmc1.docx) (1.2MB, docx) 

Statistical Analysis

[mmc2.pdf](/articles/instance/10965408/bin/mmc2.pdf) (1.2MB, pdf) 

* * *

Articles from eClinicalMedicine are provided here courtesy of **Elsevier**

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

## ACTIONS

  * [ View on publisher site ](https://doi.org/10.1016/j.eclinm.2024.102475)
  * [ PDF (1018.4 KB) ](pdf/main.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://pmc.ncbi.nlm.nih.gov/articles/PMC11231910/
scrape_date: 2025-02-28T17:08:52.984130
content_type: markdown
hash: 9e2ad35ebd0b72287997a9d1ca8548e5162e16a45741580ea5bbf16fa9aea5a3
title:
            Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity - 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/10.1001/jamainternmed.2024.2525 "View on publisher site")
  *   *   * ## 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/)

![JAMA Network logo](https://cdn.ncbi.nlm.nih.gov/pmc/banners/logo-jamasd.png)

JAMA Intern Med

. 2024 Jul 8;184(9):1056–1064. doi: [10.1001/jamainternmed.2024.2525](https://doi.org/10.1001/jamainternmed.2024.2525)

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



# Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity

[Patricia J Rodriguez](https://pubmed.ncbi.nlm.nih.gov/?term=%22Rodriguez%20PJ%22%5BAuthor%5D)

###  Patricia J Rodriguez, PhD

1Truveta Inc, Bellevue, Washington

Find articles by [Patricia J Rodriguez](https://pubmed.ncbi.nlm.nih.gov/?term=%22Rodriguez%20PJ%22%5BAuthor%5D)

1, [Brianna M Goodwin Cartwright](https://pubmed.ncbi.nlm.nih.gov/?term=%22Goodwin%20Cartwright%20BM%22%5BAuthor%5D)

###  Brianna M Goodwin Cartwright, MS

1Truveta Inc, Bellevue, Washington

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

1, [Samuel Gratzl](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gratzl%20S%22%5BAuthor%5D)

###  Samuel Gratzl, PhD

1Truveta Inc, Bellevue, Washington

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

1, [Rajdeep Brar](https://pubmed.ncbi.nlm.nih.gov/?term=%22Brar%20R%22%5BAuthor%5D)

###  Rajdeep Brar, MD

1Truveta Inc, Bellevue, Washington

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

1, [Charlotte Baker](https://pubmed.ncbi.nlm.nih.gov/?term=%22Baker%20C%22%5BAuthor%5D)

###  Charlotte Baker, DrPH

1Truveta Inc, Bellevue, Washington

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

1, [Ty J Gluckman](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gluckman%20TJ%22%5BAuthor%5D)

###  Ty J Gluckman, MD

2Center for Cardiovascular Analytics, Research and Data Science (CARDS), Providence Heart Institute, Providence Health System, Portland, Oregon

Find articles by [Ty J Gluckman](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gluckman%20TJ%22%5BAuthor%5D)

2, [Nicholas L Stucky](https://pubmed.ncbi.nlm.nih.gov/?term=%22Stucky%20NL%22%5BAuthor%5D)

###  Nicholas L Stucky, MD

1Truveta Inc, Bellevue, Washington

Find articles by [Nicholas L Stucky](https://pubmed.ncbi.nlm.nih.gov/?term=%22Stucky%20NL%22%5BAuthor%5D)

1,✉

  * Author information
  * Article notes
  * Copyright and License information



1Truveta Inc, Bellevue, Washington

2Center for Cardiovascular Analytics, Research and Data Science (CARDS), Providence Heart Institute, Providence Health System, Portland, Oregon

**Accepted for Publication:** April 14, 2024.

**Published Online:** July 8, 2024. doi:[10.1001/jamainternmed.2024.2525](https://doi.org/10.1001/jamainternmed.2024.2525)

**Open Access:** This is an open access article distributed under the terms of the [CC-BY-NC-ND License](https://jamanetwork.com/pages/cc-by-nc-nd-license-permissions). © 2024 Rodriguez PJ et al. _JAMA Internal Medicine_.

✉

**Corresponding Author:** Nicholas L. Stucky, MD, Truveta Inc, 1745 114th Ave SE, Bellevue, WA 98004 (nicholass@truveta.com).

**Author Contributions:** Drs Rodriguez and Stucky had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

_Concept and design:_ Rodriguez, Baker, Gluckman, Stucky.

_Acquisition, analysis, or interpretation of data:_ Rodriguez, Cartwright, Gratzl, Brar, Gluckman, Stucky.

_Drafting of the manuscript:_ Rodriguez, Gluckman, Stucky.

_Critical review of the manuscript for important intellectual content:_ Rodriguez, Cartwright, Gratzl, Brar, Baker, Stucky.

_Statistical analysis:_ Rodriguez, Cartwright.

_Obtained funding:_ Stucky.

_Administrative, technical, or material support:_ Rodriguez, Gratzl, Baker, Gluckman, Stucky.

_Supervision:_ Gluckman, Stucky.

**Conflict of Interest Disclosures:** Dr Gluckman reported consulting fees from Premier outside the submitted work. No other disclosures were reported.

**Data Sharing Statement:** See Supplement 3.

**Additional Contributions:** The authors thank Elisabetta Patorno, MD, Brigham and Women’s Hospital, Boston, for her substantial contributions to the study design. Dr Patorno was not compensated.

✉

Corresponding author.

Received 2023 Dec 14; Accepted 2024 Apr 14; Issue date 2024 Sep.

Copyright 2024 Rodriguez PJ et al. _JAMA Internal Medicine_.

This is an open access article distributed under the terms of the CC-BY-NC-ND License.

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

PMCID: PMC11231910 PMID: [38976257](https://pubmed.ncbi.nlm.nih.gov/38976257/)

See "[Tirzepatide for Weight Reduction in Chinese Adults With Obesity](/articles/PMC11337071/)" in _JAMA_ , volume 332 on page 551.

## Key Points

### Question

How does weight loss differ between patients receiving tirzepatide compared with semaglutide among a clinical population of adults with overweight or obesity?

### Findings

In this cohort study of 18 386 propensity-score matched patients initiating tirzepatide or semaglutide labeled for type 2 diabetes, discontinuation was common; most achieved weight loss of 5% or greater within 1 year of treatment.

### Meaning

Although most adults with overweight or obesity experienced 5% or greater weight loss with treatment, the benefit was greater with tirzepatide.

* * *

This cohort study compares treatment-associated weight loss and rates of gastrointestinal adverse events among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes in a clinical setting.

## Abstract

### Importance

Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available.

### Objective

To compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting.

### Design, Setting, and Participants

In this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes through November 3, 2023, were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The analysis was completed on April 3, 2024.

### Exposures

Tirzepatide or semaglutide in formulations labeled for T2D, on or off label.

### Main Outcomes and Measures

On-treatment weight change in a propensity score–matched population, assessed as hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared.

### Results

Among 41 222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 18 386 remained after propensity score matching. The mean (SD) age was 52.0 (12.9) years, 12 970 were female (70.5%), 14 182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5140 patients (55.9%) receiving tirzepatide and 4823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, −2.4%; 95% CI −2.5% to −2.2%), 6 months (difference, −4.3%; 95% CI, −4.7% to −4.0%), and 12 months (difference, −6.9%; 95% CI, −7.9% to −5.8%). Rates of gastrointestinal AEs were similar between groups.

### Conclusions and Relevance

In this population of adults with overweight or obesity, use of tirzepatide was associated with significantly greater weight loss than semaglutide. Future study is needed to understand differences in other important outcomes.

## Introduction

Overweight and obesity are highly prevalent conditions associated with increased morbidity and mortality.1,2,3 Historically, pharmacologic treatments for weight reduction (antiobesity medications [AOMs]) have been limited in number, not particularly well-tolerated, and modest in impacts on weight.4,5 However, newer therapies, including the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide and the dual GLP-1 RA/gastric inhibitory polypeptide (GIP) agonist tirzepatide, have demonstrated substantial weight reduction in patients with obesity, with and without type 2 diabetes (T2D), in randomized clinical trials (RCTs).6,7,8,9,10

While tirzepatide produces greater weight loss than semaglutide in patients with T2D,11 data from head-to-head trials comparing these therapies in patients with overweight or obesity are not yet available. Further, it remains unclear whether the magnitude of weight loss in clinical settings mirrors that in RCTs, given well-described differences between these populations.12,13,14 Finally, because these medications are costly and insurance coverage is limited for patients without T2D, actual adherence may differ from clinical trials, potentially attenuating the treatment effect.

Accordingly, we aimed to compare on-treatment weight change between tirzepatide and semaglutide (injectable) labeled for T2D in a large clinical population. We quantified differences in (1) likelihood of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and (2) percentage change in body weight at 3, 6, and 12 months with treatment.

## Methods

### Study Design

New users of tirzepatide or semaglutide with overweight or obesity (regardless of T2D) were included in the study. The first dispensation of tirzepatide or semaglutide was considered the treatment initiation date and served as the study index date. New users were defined as those having no previous dispensation of any GLP-1 RA or GLP-1 RA/GIP agonist (henceforth referred to as GLP-1 RA for brevity). Only adult patients with regular interactions with the health care system and an available baseline weight were included (see Study Population below). Patients were followed up for weight loss and gastrointestinal adverse events (AEs) until the first of discontinuation of therapy, GLP-1 RA switching, administrative censoring, or study end (November 3, 2023).

### Data

This study used a subset of Truveta data. Truveta provides access to continuously updated and linked electronic health record (EHR) from a collective of US health care systems, including structured information on demographics (age, sex, health system–reported race and ethnicity), encounters, diagnoses, vital signs (eg, weight, body mass index [BMI, calculated as weight in kilograms divided by height in meters squared], blood pressure), medication requests (prescriptions), laboratory and diagnostic tests and results (eg, hemoglobin A1c [HbA1c] tests and values), and procedures. In addition to EHR data for care delivered within Truveta constituent health care systems, medication dispensing and social drivers of health (SDOH) information are made available through linked third-party data. Medication dispense (via e-prescribing data) includes fills for prescriptions written both within and outside constituent health care systems, providing greater observability into patients’ medication history. Medication dispense histories are updated at encounters, and include fill dates, NDC or RxNorm codes, quantity dispensed, and days of medication supplied. SDOH data include individual income and education.

Data are normalized into a common data model through syntactic and semantic normalization. Truveta data are then deidentified by expert determination under the Health Insurance Portability and Accountability Act Privacy Rule and therefore exempt from institutional review board approval. Data for this study were accessed on November 3, 2023, using Truveta Studio.

This retrospective observational cohort study followed the Strengthening the Reporting of Observational Studies in Epidemiology ([STROBE](http://www.equator-network.org/reporting-guidelines/strobe/)) reporting guidelines.15 The analysis was completed on April 3, 2024.

### Study Population, Setting, and Exposure

We identified adults first dispensed tirzepatide or semaglutide labeled for T2D (as brand names Mounjaro [Eli Lilly] or Ozempic [Novo Nordisk], respectively) between May 1, 2022 (the month of tirzepatide approval) and September 30, 2023, and who had overweight (BMI ≥27 or a diagnosis code indicating BMI ≥27) or obesity (BMI ≥30 or a diagnosis code for obesity) in the year before their index date. An overweight threshold BMI of 27 or greater was used to mirror clinical trials in patients with overweight or obesity.6,7,9,10 We required a complete negative history of GLP-1 RA use. To improve outcome observability, we limited our analysis to patients with regular interactions with the health care system during the year prior to their index date, defined as at least 1 encounter, observation, or medication request in each consecutive 6-month period preceding the index date. We required a GLP-1 RA prescription and a baseline weight measurement in the 60 days before the index date. A 60-day window was selected because insurance denials and appeal processes for these medications may result in unusually long times between medication prescribing and filling. Of note, the GLP-1 RA prescribed was not required to match the medication first dispensed, given that drug shortages during the study period16,17 may have resulted in substitutions. Patients were categorized according to the medication dispensed. Additional exclusions were made for patients with missing sex and those with no follow-up time. The number of patients meeting the inclusion criteria determined the sample size. Codes for all definitions used in this study are provided in Supplement 1 (eDefinitions).

We relied on brand as a proxy for target dose. The standard full dose is 0.5 mg for semaglutide labeled for T2D and 5.0 mg for tirzepatide (labeled exclusively for T2D at the time of this analysis). The standard dose escalation schedule for both drugs is 4 weeks.

### Patient Comorbidities and Covariates

Patients were classified as having T2D if they had a T2D diagnosis, were prescribed, administered, or dispensed insulin or a dipeptidyl peptidase 4 (DPP-4) inhibitor, or had an HbA1c level of 7.5% or greater in the 2 years before their index date. Baseline patient demographics, clinical comorbidities, use of other antidiabetic medication (ADM) and AOM, and history of bariatric surgery in the 2 years before the index date were assessed. Several steps were taken to standardize weight data, including the removal of apparent data entry or unit conversion errors (detailed in eMethods 1.1 in Supplement 2). The most recent weight within the 60 days before the index date was considered the baseline value.

### Weight Outcomes

Our primary estimand of interest was on-treatment weight loss. Therefore, patients were censored at the first of either treatment discontinuation (≥30 days without medication on hand), GLP-1 RA switching (change to a different medication; brand changes were allowed), last encounter, or study end (November 3, 2023). Analyses assumed unobserved weights for at-risk patients were missing at random, and therefore conditional on observed information only. Although relationships with unobserved variables cannot be tested, we assessed characteristics of patients with vs without any follow-up weight.

Propensity scores were used to balance treatment groups on measured variables. Propensity scores estimated the probability of initiating tirzepatide, compared to semaglutide, as a function of demographic, clinical, and utilization characteristics (eMethods 1.2 in Supplement 2). Patients were then matched using 1:1 nearest neighbor propensity score (PS) matching. Balance was assessed by standardized mean differences, with an acceptable threshold of 0.1. To provide further control for residual confounding, age, presence of T2D (eg, on-label use), and baseline weight were included as covariates in all parametric and semiparametric models.

Percentage change in body weight was calculated as (follow-up weight − baseline weight)/baseline weight. Probabilities of achieving 5% or greater, 10% or greater, and 15% or greater weight loss within 1 year, accounting for censoring, were extracted from Kaplan-Meier models. Relative differences in the hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss for those receiving tirzepatide compared with semaglutide were estimated using Cox proportional hazards models with a robust variance estimator.18 Survival methods were used to accommodate censoring rates in this clinical dataset.

For weight change at 3, 6, and 12 months, only the subpopulation still at risk (not yet censored) at the time point of interest was evaluated. The weight value nearest to the time point, within 45 days, was considered the outcome value. For at-risk patients without a weight value in this window, multiple imputation was used to impute weight change using information on all measured covariates and outcomes from the full at-risk population. Within each (_m_ = 10) imputed dataset of at-risk patients at the time point of interest, propensity score matching was reapplied, and differences in percentages of weight loss were estimated using linear models. Estimates were then pooled across imputations using Rubin rules.19 Details on missingness and imputation are provided in eMethods 1.3 to 1.5 in Supplement 2 (eTable 1, eTable 2, eTable 3 in Supplement 2).

### Sensitivity Analyses

Several sensitivity analyses were performed to test the robustness of findings. First, we replicated all analyses using inverse probability of treatment weighting (IPTW), rather than propensity score matching. Second, we conducted stratified analyses for patients with and without T2D (eg, on-label vs off-label use), replicating the full process described for each stratum. Third, we conducted a modified intention-to-treat (ITT) analysis, where censoring time ignored discontinuation and switching. This analysis included all available follow-up weights regardless of whether the patient was receiving treatment. Finally, analyses were replicated excluding patients with missing weight values (complete case analysis). We also conducted a sensitivity analysis comparing liraglutide to semaglutide as validation.

### Safety Outcomes

Moderate to severe gastrointestinal AE (bowel obstruction, cholecystitis, cholelithiasis, gastroenteritis, gastroparesis, and pancreatitis) were identified from EHR data. Mild AEs, such as nausea and vomiting, were not included given the expectation of inconsistent capture in EHR data. The incidence rate of each gastrointestinal AE per 1000 person-years at risk was calculated, using the previously described censoring approach. Patients with a history of the specific AE in the year before index were excluded from analyses of the specific AE. Differences in the hazard of each AE between tirzepatide and semaglutide were estimated using Cox proportional hazards models.

### Stats Program and Packages Used

Analyses were conducted in R statistical software (version 4.2.3; R Foundation) using the following packages: rlang,20 arrow,21 dplyr,22 tidyr,23 lubridate,24 forcats,25 table1,26 cobalt,27 MatchIt,28 WeightIt,29 mice,30 MatchThem,31 survey,32 survival,33 ggsurvfit,34 broom,35 ggplot2,36 and xtable.37

## Results

### Patient Characteristics

In total, 41 222 patients met our inclusion criteria (tirzepatide: 9193; semaglutide: 32 029) (Figure 1). Prior to propensity score matching, patients who initiated tirzepatide, compared with semaglutide, were younger and a higher proportion were female, White, and had evidence of college education (Table). Patients who initiated tirzepatide had a lower prevalence of T2D and most other comorbidities. Despite demographic and clinical differences, mean (SD) baseline weight was similar between groups (tirzepatide: 110 [25.7] kg; semaglutide: 109 [25.2] kg), with measurement occurring an average (median) of 9.3 (4.0; interquartile range [IQR], 14-1; difference, 13) days before treatment initiation. The 1:1 propensity score matched cohort included 18 386 patients, with standardized mean differences for all variables lower than 0.1.

#### Figure 1. Study Flow Diagram.

[![Figure 1. ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/131e/11231910/107b009b7cb3/jamainternmed-e242525-g001.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=11231910_jamainternmed-e242525-g001.jpg)

[Open in a new tab](figure/ioi240039f1/)

A complete negative history of glucagon-like peptide 1 receptor agonist (GLP-1 RA) dispensing was required before the index date. Other exclusions include missing sex and no follow-up time. GLP-1 RA refers to both GLP-1 RA and GLP-1 RA/gastric inhibitory polypeptide agonist medications.

aIndex event: first GLP-1 dispensed between May 2022 to September 2023.

#### Table. Characteristics of Study Population Before and After Propensity Score Matchinga.

Variable | No. (%)  
---|---  
Before matching | After matching  
Tirzepatide (n = 9193) | Semaglutide (n = 32 029) | Overall (n = 41 222) | Tirzepatide (n = 9193) | Semaglutide (n = 9192) | Overall (n = 18 386) | Absolute SMD  
Age | 51.9 (12.7) | 56.4 (13.0) | 55.4 (13.1) | 51.9 (12.7) | 52.0 (13.2) | 52.0 (12.9) | .01  
Sex |  |  |  |  |  |  |   
Female | 6484 (70.5) | 21 060 (65.8) | 27 544 (66.8) | 6484 (70.5) | 6486 (70.6) | 12 970 (70.5) | <.001  
Male | 2709 (29.5) | 10 969 (34.2) | 13 678 (33.2%) | 2709 (29.5) | 2707 (29.4) | 5416 (29.5) | <.001  
Race |  |  |  |  |  |  |   
Asian | 156 (1.7) | 880 (2.7) | 1036 (2.5) | 156 (1.7) | 198 (2.2) | 354 (1.9) | .005  
Black | 1050 (11.4) | 4481 (14.0) | 5531 (13.4) | 1050 (11.4) | 1121 (12.2) | 2171 (11.8) | .008  
White | 7097 (77.2) | 23 559 (73.6) | 30 656 (74.4) | 7097 (77.2) | 7085 (77.1) | 14 182 (77.1) | .001  
Other or unknownb | 890 (9.7) | 3109 (9.7) | 3999 (9.7) | 890 (9.7) | 789 (8.6) | 1679 (9.1) | .01  
Ethnicity |  |  |  |  |  |  |   
Hispanic or Latino | 1414 (15.4) | 4252 (13.3) | 5666 (13.7) | 1414 (15.4) | 1374 (14.9) | 2788 (15.2) | .01  
Not Hispanic or Latino | 7355 (80.0) | 26 093 (81.5) | 33 448 (81.1) | 7355 (80.0) | 7416 (80.7) | 14 771 (80.3) | .007  
Other | 424 (4.6) | 1684 (5.3) | 2108 (5.1) | 424 (4.6) | 403 (4.4) | 827 (4.5) | .002  
Education: any college on record | 5467 (59.5) | 14 275 (44.6) | 19 742 (47.9) | 5467 (59.5) | 5463 (59.4) | 10 930 (59.4) | <.001  
Income range, $ |  |  |  |  |  |  |   
0-25 000 | 220 (2.4) | 853 (2.7) | 1073 (2.6) | 220 (2.4) | 290 (3.2) | 510 (2.8) | .008  
25 001-50 000 | 3763 (40.9) | 14 602 (45.6) | 18 365 (44.6) | 3763 (40.9) | 3851 (41.9) | 7614 (41.4) | .01  
50 001-80 000 | 3521 (38.3) | 11 376 (35.5) | 14 897 (36.1) | 3521 (38.3) | 3423 (37.2) | 6944 (37.8) | .01  
>80 000 | 1490 (16.2) | 4354 (13.6) | 5844 (14.2) | 1490 (16.2) | 1428 (15.5) | 2918 (15.9) | .007  
Unknown | 199 (2.2) | 844 (2.6) | 1043 (2.5) | 199 (2.2) | 201 (2.2) | 400 (2.2) | <.001  
State |  |  |  |  |  |  |   
Texas | 3997 (43.5) | 9397 (29.3) | 13 394 (32.5) | 3997 (43.5) | 3969 (43.2) | 7966 (43.3) | .006  
Wisconsin | 591 (6.4) | 2850 (8.9) | 3441 (8.3) | 591 (6.4) | 582 (6.3) | 1173 (6.4) | .004  
Illinois | 583 (6.3) | 3239 (10.1) | 3822 (9.3) | 583 (6.3) | 586 (6.4) | 1169 (6.4) | .001  
Ohio | 906 (9.9) | 2425 (7.6) | 3331 (8.1) | 906 (9.9) | 917 (10.0) | 1823 (9.9) | .004  
Washington | 458 (5.0) | 3538 (11.0) | 3996 (9.7) | 458 (5.0) | 457 (5.0) | 915 (5.0) | <.001  
California | 754 (8.2) | 3021 (9.4) | 3775 (9.2) | 754 (8.2) | 750 (8.2) | 1504 (8.2) | .00  
Other | 1904 (20.7) | 7559 (23.6) | 9463 (23.0) | 1904 (20.7) | 1932 (21.0) | 3836 (20.9) | .008  
Weight, kg | 110 (25.7) | 109 (25.2) | 109 (25.3) | 110 (25.7) | 110 (25.8) | 110 (25.8) | 0.01 (25.8)  
BMIc | 39.0 (8.08) | 38.6 (7.92) | 38.7 (7.96) | 39.0 (8.08) | 39.1 (8.09) | 39.1 (8.09) | .008  
Unknown | 1202 (13.1) | 2661 (8.3) | 3863 (9.4) | 1202 (13.1) | 1211 (13.2) | 2413 (13.1) | <.001  
Years since first overweight/obesity | 4.48 (3.11) | 5.08 (3.28) | 4.95 (3.25) | 4.48 (3.11) | 4.50 (3.11) | 4.49 (3.11) | .004  
T2D | 4773 (51.9) | 22 890 (71.5) | 27 663 (67.1) | 4773 (51.9) | 4790 (52.1) | 9563 (52.0) | .004  
Years since first T2D (among patients with T2D) | 3.54 (3.21) | 4.24 (4.09) | 4.12 (3.96) | 3.54 (3.21) | 3.42 (3.36) | 3.48 (3.29) | .04  
Months since May 2022 | 8.48 (3.93) | 8.44 (4.59) | 8.45 (4.45) | 8.48 (3.93) | 8.69 (4.50) | 8.59 (4.23) | .05  
No. of HBA1c tests in previous 2 y | 2.19 (1.89) | 2.85 (2.10) | 2.71 (2.07) | 2.19 (1.89) | 2.21 (1.87) | 2.20 (1.88) | .008  
Bariatric surgery history | 385 (4.2) | 1140 (3.6) | 1525 (3.7) | 385 (4.2) | 367 (4.0) | 752 (4.1) | .002  
Comorbidities |  |  |  |  |  |  |   
Atrial fibrillation | 404 (4.4) | 2332 (7.3) | 2736 (6.6) | 404 (4.4) | 405 (4.4) | 809 (4.4) | <.001  
Asthma | 1658 (18.0) | 6253 (19.5) | 7911 (19.2) | 1658 (18.0) | 1689 (18.4) | 3347 (18.2) | .009  
CKD | 833 (9.1) | 4909 (15.3) | 5742 (13.9) | 833 (9.1) | 852 (9.3) | 1685 (9.2) | .007  
COPD | 412 (4.5) | 2471 (7.7) | 2883 (7.0) | 412 (4.5) | 416 (4.5) | 828 (4.5) | .002  
Glaucoma | 133 (1.4) | 786 (2.5) | 919 (2.2) | 133 (1.4) | 135 (1.5) | 268 (1.5) | <.001  
Heart failure | 442 (4.8) | 2852 (8.9) | 3294 (8.0) | 442 (4.8) | 452 (4.9) | 894 (4.9) | .005  
Hyperlipidemia | 5736 (62.4) | 23 839 (74.4) | 29 575 (71.7) | 5736 (62.4) | 5802 (63.1) | 11 538 (62.8) | .015  
Hypertension | 5741 (62.4) | 23 393 (73.0) | 29 134 (70.7) | 5741 (62.4) | 5747 (62.5) | 11 488 (62.5) | .001  
Ischemic heart disease | 449 (4.9) | 2600 (8.1) | 3049 (7.4) | 449 (4.9) | 446 (4.9) | 895 (4.9) | .002  
Osteoporosis | 269 (2.9) | 1318 (4.1) | 1587 (3.8) | 269 (2.9) | 281 (3.1) | 550 (3.0) | .001  
Acute MI | 161 (1.8) | 942 (2.9) | 1103 (2.7) | 161 (1.8) | 145 (1.6) | 306 (1.7) | .002  
Ischemic stroke | 12 (0.1) | 73 (0.2) | 85 (0.2) | 12 (0.1) | 7 (0.1) | 19 (0.1) | <.001  
Major depressive disorder | 2026 (22.0) | 7603 (23.7) | 9629 (23.4) | 2026 (22.0) | 2018 (22.0) | 4044 (22.0) | .002  
ADM |  |  |  |  |  |  |   
DPP4 | 659 (7.2) | 3175 (9.9) | 3834 (9.3) | 659 (7.2) | 666 (7.2) | 1325 (7.2) | .003  
Insulin | 485 (5.3) | 2634 (8.2) | 3119 (7.6) | 485 (5.3) | 488 (5.3) | 973 (5.3) | .001  
Metformin | 4179 (45.5) | 19 557 (61.1) | 23 736 (57.6) | 4179 (45.5) | 4217 (45.9) | 8396 (45.7) | .008  
SGLT2i | 1162 (12.6) | 5828 (18.2) | 6990 (17.0) | 1162 (12.6) | 1176 (12.8) | 2338 (12.7) | .005  
Sulfonylurea | 1102 (12.0) | 6274 (19.6) | 7376 (17.9) | 1102 (12.0) | 1073 (11.7) | 2175 (11.8) | .01  
AOM |  |  |  |  |  |  |   
Orlistat | 17 (0.2) | 53 (0.2) | 70 (0.2) | 17 (0.2) | 21 (0.2) | 38 (0.2) | <.001  
Phentermine topiramate | 88 (1.0) | 155 (0.5) | 243 (0.6) | 88 (1.0) | 76 (0.8) | 164 (0.9) | .001  
  
[Open in a new tab](table/ioi240039t1/)

Abbreviations: ADM, antidiabetic medication; AOM, anti-obesity medication; Black, Black or African American; BMI, body mass index; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DPP4, dipeptidyl peptidase 4 inhibitor; MI, myocardial infarction; SGLT2i, sodium/glucose cotransporter-2 inhibitor; SMD, standardized mean difference; T2D, type 2 diabetes.

a

Categorical variables expressed as No. (%). Durations (overweight/obesity and T2D) refer to time (years) since first evidence in electronic health record. Other state includes unknown and states with less than 3% of the prematch sample: Alaska, Arizona, Arkansas, Colorado, Florida, Georgia, Idaho, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Missouri, Montana, Nevada, New Mexico, North Carolina, Oklahoma, Oregon, Pennsylvania, South Carolina, Tennessee, Utah, Virginia, and unknown.

b

Other race includes American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, other race, unknown, declined to answer. Absolute SMDs are reported.

c

Calculated as weight in kilograms divided by height in meters squared.

The mean (median) duration of on-treatment follow-up was 165 (129; IQR, 75-231; difference, 156) days. Follow-up was ended by discontinuation for 9963 (54.2%) (tirzepatide: 5140 [55.9%]; semaglutide: 4823 [52.5%]), medication switching for 153 (0.8%) (tirzepatide: 124 [1.3%]; semaglutide: 29 [0.3%]), and administrative censoring for 8270 (45.0%) (tirzepatide: 3929 [42.7%]; semaglutide: 4341 [47.2%]). The mean (median) duration of follow-up with administrative censoring alone (modified ITT analysis) was 257 (256) days. Distributions of initiation and follow-up times are provided in eFigure 1 and eFigure 2 in Supplement 2.

Overall, 31 419 (76%) patients had at least 1 on-treatment follow-up weight and 35 097 (85%) had at least 1 follow-up weight during observation (eTable 3 in Supplement 2). The mean (median) days between weight observations on-treatment was 37.6 (27) (during observation, 62.5 [50]) for tirzepatide and 37.6 (27) (during observation, 59.1 [46]) for semaglutide.

### Hazard of 5%, 10%, and 15% Weight Loss

Among the matched population at risk (undergoing treatment), 81.8% (95% CI, 79.8%-83.7%) receiving tirzepatide vs 66.5% (95% CI, 64.3%-68.7%) receiving semaglutide achieved 5% or greater weight loss, 62.1% (95% CI, 59.7%-64.3%) vs 37.1% (95% CI, 34.6%-39.4%) achieved 10% or greater weight loss, and 42.3% (95% CI, 39.8%-44.6%) vs 18.1% (95% CI, 16.1%-20.0%) achieved 15% or greater weight loss within 365 days (Figure 2). HRs comparing tirzepatide with semaglutide were 1.76 (95% CI, 1.68-1.84) for 5% or greater weight loss, 2.54 (95% CI, 2.37-2.73) for 10% weighor greatert loss and 3.24 (95% CI, 2.91-3.61) for 15% or greater weight loss (Figure 3).

#### Figure 2. Event Probabilities for 5% or Greater, 10% or Greater, and 15% or Greater Weight Reduction Among Propensity-Score Matched Patients on Treatment.

![Figure 2. ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/131e/11231910/49d42c280cd7/jamainternmed-e242525-g002.jpg)

[Open in a new tab](figure/ioi240039f2/)

The y-axis represents the event probability (1-survival probability [eg, probability of being event-free]).

#### Figure 3. Mean Percentage Change in Body Weight at 3, 6, and 12 Months Receiving Treatment for the Overall Population, Those With Type 2 Diabetes (T2D), and Those Without T2D.

![Figure 3. ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/131e/11231910/ff9ab52422ae/jamainternmed-e242525-g003.jpg)

[Open in a new tab](figure/ioi240039f3/)

Bars represent mean changes in body weight from baseline to the time point among the propensity score matched population of patients still receiving treatment. The whiskers represent 95% CIs.

### Percentage Change in Body Weight

The mean on-treatment change in body weight was −5.9% (95% CI, −6.0% to −5.8%) for tirzepatide vs −3.6% (95% CI, −3.7% to −3.4%) for semaglutide at 3 months, −10.1% (95% CI, −10.4% to −9.9%) vs −5.8% (95% CI, −6.0% to −5.5%) at 6 months, and −15.3% (95% CI, −16.0% to −14.5%) vs −8.3% (95% CI, −9% to −7.6%) at 12 months (Figure 4). After adjusting for residual confounding, the absolute difference in weight loss between tirzepatide and semaglutide was −2.4% (95% CI, −2.5% to −2.2), −4.3% (95% CI, −4.7% to −4.0%), and −6.9% (95% CI, −7.9% to −5.8%) at 3, 6, and 12 months receiving treatment, respectively (Figure 3).

#### Figure 4. Treatment Effects Comparing Tirzepatide to Semaglutide for All Patients, Patients With Type 2 Diabetes (T2D), and Patients Without T2D.

![Figure 4. ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/131e/11231910/a088baa72081/jamainternmed-e242525-g004.jpg)

[Open in a new tab](figure/ioi240039f4/)

Points represent point estimates; the whiskers represent 95% CIs. Panels A-C contain hazard ratios for achieving 5% or greater, 10% or greater, and 15% or greater weight loss for patients receiving tirzepatide vs semaglutide among propensity score matched populations. Hazard ratios greater than 1 indicate higher likelihood of reaching weight loss threshold with tirzepatide. Panels D-F contain absolute differences in body weight change at 3 months, 6 months, and 12 months for patients receiving tirzepatide vs semaglutide among propensity score matched populations still receiving treatment at the time point. Negative differences indicate greater weight loss with tirzepatide.

### Sensitivity Analyses

Modified ITT analyses resulted in fewer patients achieving weight loss thresholds, smaller weight reductions, and slightly attenuated comparative effect estimates, though tirzepatide remained associated with significantly greater weight loss in all analyses (eResults 2.1, eFigure 3, eFigure 4, eFigure 5, and eFigure 6 in Supplement 2). A smaller proportion achieved 5% or greater weight loss within 1 year, 71.1% (95% CI, 69.9%-72.3%) with tirzepatide and 56.4% (95% CI, 55%-57.8%) with semaglutide, resulting in an HR of 1.63 (95% CI, 1.56-1.70). Similarly, mean changes in body weight were smaller: −5.3% (95% CI, −5.4% to −5.2%) for tirzepatide vs −3.3% (95% CI, −3.4% to −3.2%) for semaglutide at 3 months, −8.2% (95% CI, −8.4% to −8.0%) for tirzepatide vs −5.0% (95% CI, −5.1% to −4.8%) for semaglutide at 6 months, and −11.4% (95% CI, −12.0% to −10.8%) for tirzepatide vs −6.2% (95% CI, −6.7% to −5.8%) for semaglutide at 12 months. After adjusting for residual confounding, the difference in weight loss between those receiving tirzepatide vs semaglutide was −2.0% (95% CI, −2.1% to −1.8%) at 3 months, −3.2% (95% CI, −3.5% to −3.0%) at 6 months, and −5.1% (95% CI, −5.8% to −4.3%) at 12 months.

Sensitivity analyses using inverse probability of treatment weighting produced very similar results (eFigure 4 and eFigure 6 in Supplement 2). Results of the liraglutide validation analysis are given in eFigure 7, eFigure 8, eFigure 9, and eFigure 10 in Supplement 2.

### Subgroup Analyses

In stratified analyses, those without T2D had larger reductions in body weight than those with T2D for tirzepatide and semaglutide alike (Figure 3; eFigures 11 and 12 in Supplement 2). Tirzepatide was still associated with significantly greater weight loss in all analyses (eFigure 13 and eFigure 14 in Supplement 2).

### Gastrointestinal Adverse Events

We observed no significant differences in the risk of any gastrointestinal AEs between those receiving tirzepatide vs semaglutide (eTable 4 in Supplement 2).

## Discussion

In this large clinical analysis of US adults with overweight or obesity who initiated tirzepatide or semaglutide treatment, those receiving tirzepatide were more likely to achieve 5% or greater, 10% or greater, and 15% or greater weight loss and experienced larger reductions in body weight at 3, 6, and 12 months. To our knowledge, this study represents the first clinical comparative effectiveness study of tirzepatide and semaglutide in adults with overweight or obesity. Comparative effect estimates were consistent in direction and significance between methodological approaches (propensity score matching, IPTW, modified ITT) and within subgroups of patients with and without T2D. No significant differences in the incidence of gastrointestinal AEs were observed.

Findings in this study are broadly consistent with existing evidence from RCTs. Among placebo-controlled trials of patients with overweight or obesity, treatment with tirzepatide at 10 mg per week resulted in 82% and 96% of individuals with and without T2D achieving 5% or more weight loss by 72 weeks, respectively (efficacy estimands).9,10 Among similarly designed placebo-controlled trials, treatment with semaglutide at 2.4 mg per week resulted in 73% and 92% of individuals with and without T2D achieving 5% or greater body weight by 68 weeks, respectively (efficacy estimands).6,7 While data from head-to-head trials are more limited, a single study that evaluated the glucose-lowering effect of tirzepatide (5 mg per week) compared with semaglutide (1 mg per week) in patients with T2D found that 5% weight loss was achieved by 69% and 58%, respectively.11 Importantly, a trial comparing tirzepatide to semaglutide in patients with overweight or obesity, but without T2D is underway (SURMOUNT-5, [NCT05822830](https://clinicaltrials.gov/ct2/show/NCT05822830))38; the results, however, are not expected until late 2024.

### Strengths and Limitations

This study has several strengths. First, the analysis included a large and recent cohort of patients with overweight and obesity evaluated in May 2022 (the month of tirzepatide approval) or later. It is likely that the weight reduction observed in our study was greater than that found in previous clinical studies of GLP-1 RA because such studies ended before semaglutide and/or tirzepatide were available.39,40 Second, estimates were consistent in direction and significance between estimands (on treatment vs modified ITT), subgroups (with vs without T2D), and methodological approaches (propensity score matching, IPTW, complete case analysis). Third, this study included individuals likely ineligible for participation in related RCTs, including those with major depressive disorder. Major depressive disorder was common in our population (4044 patients [22%] had a history in the preceding 2 years) suggesting clinical trials may have excluded many patients using these medications in clinical settings. Finally, use of prescribing and dispensing data allowed us to include populations without T2D, which may not be captured in pharmacy claims data alone given limited insurance coverage for off-label use.

Our study is also subject to several limitations. Unlike many clinical end points, weight loss is directly observable to patients, which may result in informative censoring, with those observing no weight loss being more likely to discontinue or switch drugs.40,41 Whereas a modified ITT analysis inclusive of postdiscontinuation weights showed smaller reductions in weight, differences between tirzepatide and semaglutide were similar. In addition, unmeasured confounding, especially the degree of motivation for weight loss, may exist. A substantial amount of unmeasured confounding, though, would be required to negate the treatment effect estimates observed in this study. This study used clinical EHR data, which has some inherent limitations. Information is collected during routine clinical care, and AEs are likely underreported relative to protocolized, prospective AE ascertainment in clinical trials. Similarly, weight changes are ascertained only when patients return for visits, and therefore observed event times are likely delayed relative to true times. However, we expect misclassification of AE and weight loss occurrence and timing to be nondifferential between groups, given the similarity of follow-up cadence between groups. Our imputation model assumed missingness was conditional on observed information only (eg, missing at random), which may be biased if unmeasured variables contributed to missingness. In addition, we relied on brand as a proxy for target dose because this approach most closely approximates randomization to a treatment arm, where the individual dose received may deviate from the target dose. Patients in both groups may receive doses that are higher or lower than standard full doses. Health system and payer information were unavailable for this analysis. Although the analytic sample included patients in 35 states, the geographic distribution was not representative of the US, which limited generalizability. Finally, this study included medications labeled for T2D only. Future studies are needed to compare versions labeled for weight loss.

Consistent with clinical trials, we found larger weight reductions among those without T2D, compared with those with T2D.6,7,9,10 The underlying reasons are unclear. Although differential impacts on weight are possible, patients with and without T2D may have differing motivation levels for weight loss and may engage in other weight loss activities differentially. Additional research is needed to understand the complex relationships between motivations and outcomes for patients with and without T2D. Further, most patients in our study discontinued. Additional research on discontinuation is needed, including the role of shortages, adverse events, and costs.

## Conclusions

In this large, propensity-matched, cohort study, individuals with overweight or obesity treated with tirzepatide were significantly more likely to achieve clinically meaningful weight loss and larger reductions in body weight compared with those treated with semaglutide. Consistent treatment effect estimates were observed in subgroups with and without T2D. Future work is needed to compare the effect of tirzepatide and semaglutide on other key end points (eg, reduction in major adverse cardiovascular events).42,43

Supplement 1.

eDefinitions

[jamainternmed-e242525-s001.pdf](/articles/instance/11231910/bin/jamainternmed-e242525-s001.pdf) (387.3KB, pdf) 

Supplement 2.

eMethods

eFigure 1. Distribution of initiation time by group

eFigure 2. Distribution of follow-up time by initiation date

eTable 1. Weight Availability at t: On-Treatment Analyses

eTable 2. Weight Availability at t: ITT Analyses

eTable 3. Characteristics of Matched Patients with Available vs. Missing Follow-up Weight.

eResults

eFigure 3. Proportion of at-risk patients achieving weight loss targets by one year for on treatment and intention to treat analyses

eFigure 4. Hazard ratio comparing tirzepatide vs semaglutide for achieving weight loss targets under different analytic approaches

eFigure 5. Mean change in body weight for tirzepatide and semaglutide groups under on treatment and modified intention to treat analyses

eFigure 6. Difference in percent change in body weight comparing tirzepatide to semaglutide under different analytic approaches

eFigure 7. Event probabilities of weight loss, accounting for censoring, for patients on liraglutide and semaglutide

eFigure 8. Hazard ratios comparing liraglutide to semaglutide

eFigure 9. Mean change in body weight for liraglutide and semaglutide

eFigure 10. Difference in percent change in body weight comparing liraglutide to semaglutide

eFigure 11. Weight loss event probabilities, accounting for censoring, for patients with T2D

eFigure 12. Weight loss event probabilities, accounting for censoring, for patients without T2D

eFigure 13. Hazard ratio comparing tirzepatide to semaglutide for different populations

eFigure 14. Difference in percent change in body weight comparing tirzepatide to semaglutide for different populations

eTable 4. Gastrointestinal Adverse Event Rates Per 1000 person-years

[jamainternmed-e242525-s002.pdf](/articles/instance/11231910/bin/jamainternmed-e242525-s002.pdf) (2.2MB, pdf) 

Supplement 3.

Data Sharing Statement

[jamainternmed-e242525-s003.pdf](/articles/instance/11231910/bin/jamainternmed-e242525-s003.pdf) (11KB, pdf) 

## References

  * 1.Ogden CL, Fakhouri TH, Carroll MD, et al. Prevalence of obesity among adults, by household income and education - United States, 2011-2014. MMWR Morb Mortal Wkly Rep. 2017;66(50):1369-1373. doi: 10.15585/mmwr.mm6650a1  [[DOI](https://doi.org/10.15585/mmwr.mm6650a1)] [[PMC free article](/articles/PMC5751581/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/29267260/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=MMWR%20Morb%20Mortal%20Wkly%20Rep&title=Prevalence%20of%20obesity%20among%20adults,%20by%20household%20income%20and%20education%20-%20United%20States,%202011-2014&volume=66&issue=50&publication_year=2017&pages=1369-1373&pmid=29267260&doi=10.15585/mmwr.mm6650a1&)]
  * 2.Raisi-Estabragh Z, Kobo O, Mieres JH, et al. Racial disparities in obesity-related cardiovascular mortality in the United States: temporal trends from 1999 to 2020. J Am Heart Assoc. 2023;12(18):e028409. doi: 10.1161/JAHA.122.028409  [[DOI](https://doi.org/10.1161/JAHA.122.028409)] [[PMC free article](/articles/PMC10547286/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/37671611/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Am%20Heart%20Assoc&title=Racial%20disparities%20in%20obesity-related%20cardiovascular%20mortality%20in%20the%20United%20States:%20temporal%20trends%20from%201999%20to%202020&volume=12&issue=18&publication_year=2023&pages=e028409&pmid=37671611&doi=10.1161/JAHA.122.028409&)]
  * 3.Wing RR, Lang W, Wadden TA, et al. ; Look AHEAD Research Group . Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011;34(7):1481-1486. doi: 10.2337/dc10-2415  [[DOI](https://doi.org/10.2337/dc10-2415)] [[PMC free article](/articles/PMC3120182/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21593294/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Diabetes%20Care&title=Benefits%20of%20modest%20weight%20loss%20in%20improving%20cardiovascular%20risk%20factors%20in%20overweight%20and%20obese%20individuals%20with%20type%202%20diabetes&volume=34&issue=7&publication_year=2011&pages=1481-1486&pmid=21593294&doi=10.2337/dc10-2415&)]
  * 4.Fujioka K. Safety and tolerability of medications approved for chronic weight management. Obesity (Silver Spring). 2015;23(S1)(suppl 1):S7-S11. doi: 10.1002/oby.21094  [[DOI](https://doi.org/10.1002/oby.21094)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/25900872/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Obesity%20\(Silver%20Spring\)&title=Safety%20and%20tolerability%20of%20medications%20approved%20for%20chronic%20weight%20management&volume=23&issue=S1&publication_year=2015&pages=S7-S11&pmid=25900872&doi=10.1002/oby.21094&)]
  * 5.Samaranayake NR, Ong KL, Leung RYH, Cheung BMY. Management of obesity in the National Health and Nutrition Examination Survey (NHANES), 2007-2008. Ann Epidemiol. 2012;22(5):349-353. doi: 10.1016/j.annepidem.2012.01.001  [[DOI](https://doi.org/10.1016/j.annepidem.2012.01.001)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22305325/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Ann%20Epidemiol&title=Management%20of%20obesity%20in%20the%20National%20Health%20and%20Nutrition%20Examination%20Survey%20\(NHANES\),%202007-2008&volume=22&issue=5&publication_year=2012&pages=349-353&pmid=22305325&doi=10.1016/j.annepidem.2012.01.001&)]
  * 6.Wilding JPH, Batterham RL, Calanna S, et al. ; STEP 1 Study Group . Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi: 10.1056/NEJMoa2032183  [[DOI](https://doi.org/10.1056/NEJMoa2032183)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33567185/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Once-weekly%20semaglutide%20in%20adults%20with%20overweight%20or%20obesity&volume=384&issue=11&publication_year=2021&pages=989-1002&pmid=33567185&doi=10.1056/NEJMoa2032183&)]
  * 7.Davies M, Færch L, Jeppesen OK, et al. ; STEP 2 Study Group . Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;397(10278):971-984. doi: 10.1016/S0140-6736(21)00213-0  [[DOI](https://doi.org/10.1016/S0140-6736\(21\)00213-0)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33667417/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Lancet&title=Semaglutide%202%C2%B74%20mg%20once%20a%20week%20in%20adults%20with%20overweight%20or%20obesity,%20and%20type%202%20diabetes%20\(STEP%202\):%20a%20randomised,%20double-blind,%20double-dummy,%20placebo-controlled,%20phase%203%20trial&volume=397&issue=10278&publication_year=2021&pages=971-984&pmid=33667417&doi=10.1016/S0140-6736\(21\)00213-0&)]
  * 8.Garvey WT, Batterham RL, Bhatta M, et al. ; STEP 5 Study Group . Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083-2091. doi: 10.1038/s41591-022-02026-4  [[DOI](https://doi.org/10.1038/s41591-022-02026-4)] [[PMC free article](/articles/PMC9556320/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/36216945/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Nat%20Med&title=Two-year%20effects%20of%20semaglutide%20in%20adults%20with%20overweight%20or%20obesity:%20the%20STEP%205%20trial&volume=28&issue=10&publication_year=2022&pages=2083-2091&pmid=36216945&doi=10.1038/s41591-022-02026-4&)]
  * 9.Jastreboff AM, Aronne LJ, Ahmad NN, et al. ; SURMOUNT-1 Investigators . Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi: 10.1056/NEJMoa2206038  [[DOI](https://doi.org/10.1056/NEJMoa2206038)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/35658024/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Tirzepatide%20once%20weekly%20for%20the%20treatment%20of%20obesity&volume=387&issue=3&publication_year=2022&pages=205-216&pmid=35658024&doi=10.1056/NEJMoa2206038&)]
  * 10.Garvey WT, Frias JP, Jastreboff AM, et al. ; SURMOUNT-2 investigators . Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613-626. Published online 2023. doi: 10.1016/S0140-6736(23)01200-X  [[DOI](https://doi.org/10.1016/S0140-6736\(23\)01200-X)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/37385275/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Lancet&title=Tirzepatide%20once%20weekly%20for%20the%20treatment%20of%20obesity%20in%20people%20with%20type%202%20diabetes%20\(SURMOUNT-2\):%20a%20double-blind,%20randomised,%20multicentre,%20placebo-controlled,%20phase%203%20trial&volume=402&issue=10402&publication_year=2023&pages=613-626&pmid=37385275&doi=10.1016/S0140-6736\(23\)01200-X&)]
  * 11.Frías JP, Davies MJ, Rosenstock J, et al. ; SURPASS-2 Investigators . Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. doi: 10.1056/NEJMoa2107519  [[DOI](https://doi.org/10.1056/NEJMoa2107519)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/34170647/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=N%20Engl%20J%20Med&title=Tirzepatide%20versus%20semaglutide%20once%20weekly%20in%20patients%20with%20type%202%20diabetes&volume=385&issue=6&publication_year=2021&pages=503-515&pmid=34170647&doi=10.1056/NEJMoa2107519&)]
  * 12.Johnson-Mann CN, Cupka JS, Ro A, et al. A systematic review on participant diversity in clinical trials-have we made progress for the management of obesity and its metabolic sequelae in diet, drug, and surgical trials. J Racial Ethn Health Disparities. 2023;10(6):3140-3149. doi: 10.1007/s40615-022-01487-0  [[DOI](https://doi.org/10.1007/s40615-022-01487-0)] [[PMC free article](/articles/PMC10645628/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/36536164/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Racial%20Ethn%20Health%20Disparities&title=A%20systematic%20review%20on%20participant%20diversity%20in%20clinical%20trials-have%20we%20made%20progress%20for%20the%20management%20of%20obesity%20and%20its%20metabolic%20sequelae%20in%20diet,%20drug,%20and%20surgical%20trials&volume=10&issue=6&publication_year=2023&pages=3140-3149&pmid=36536164&doi=10.1007/s40615-022-01487-0&)]
  * 13.Clark LT, Watkins L, Piña IL, et al. Increasing diversity in clinical trials: overcoming critical barriers. Curr Probl Cardiol. 2019;44(5):148-172. doi: 10.1016/j.cpcardiol.2018.11.002  [[DOI](https://doi.org/10.1016/j.cpcardiol.2018.11.002)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/30545650/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Curr%20Probl%20Cardiol&title=Increasing%20diversity%20in%20clinical%20trials:%20overcoming%20critical%20barriers&volume=44&issue=5&publication_year=2019&pages=148-172&pmid=30545650&doi=10.1016/j.cpcardiol.2018.11.002&)]
  * 14.Averitt AJ, Weng C, Ryan P, Perotte A. Translating evidence into practice: eligibility criteria fail to eliminate clinically significant differences between real-world and study populations. NPJ Digit Med. 2020;3(1):67. doi: 10.1038/s41746-020-0277-8  [[DOI](https://doi.org/10.1038/s41746-020-0277-8)] [[PMC free article](/articles/PMC7214444/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/32411828/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=NPJ%20Digit%20Med&title=Translating%20evidence%20into%20practice:%20eligibility%20criteria%20fail%20to%20eliminate%20clinically%20significant%20differences%20between%20real-world%20and%20study%20populations&volume=3&issue=1&publication_year=2020&pages=67&pmid=32411828&doi=10.1038/s41746-020-0277-8&)]
  * 15.von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative . The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453-1457. doi: 10.1016/S0140-6736(07)61602-X  [[DOI](https://doi.org/10.1016/S0140-6736\(07\)61602-X)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18064739/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Lancet&title=The%20Strengthening%20the%20Reporting%20of%20Observational%20Studies%20in%20Epidemiology%20\(STROBE\)%20statement:%20guidelines%20for%20reporting%20observational%20studies&volume=370&issue=9596&publication_year=2007&pages=1453-1457&pmid=18064739&doi=10.1016/S0140-6736\(07\)61602-X&)]
  * 16.Beba H, Ranns C, Hambling C, Diggle J, Brown P. PCDS consensus statement: a strategy for managing the supply shortage of the GLP-1 RAs ozempic and trulicity. diabetes & primary care. Diabetes and Primary Care. 2022;24(5). [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Diabetes%20and%20Primary%20Care&title=PCDS%20consensus%20statement:%20a%20strategy%20for%20managing%20the%20supply%20shortage%20of%20the%20GLP-1%20RAs%20ozempic%20and%20trulicity.%20diabetes%20&%20primary%20care&volume=24&issue=5&publication_year=2022&)]
  * 17.Whitley HP, Trujillo JM, Neumiller JJ. Special report: potential strategies for addressing GLP-1 and dual GLP-1/GIP receptor agonist shortages. Clin Diabetes. 2023;41(3):467-473. doi: 10.2337/cd23-0023  [[DOI](https://doi.org/10.2337/cd23-0023)] [[PMC free article](/articles/PMC10338283/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/37456085/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Clin%20Diabetes&title=Special%20report:%20potential%20strategies%20for%20addressing%20GLP-1%20and%20dual%20GLP-1/GIP%20receptor%20agonist%20shortages&volume=41&issue=3&publication_year=2023&pages=467-473&pmid=37456085&doi=10.2337/cd23-0023&)]
  * 18.Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33(7):1242-1258. doi: 10.1002/sim.5984  [[DOI](https://doi.org/10.1002/sim.5984)] [[PMC free article](/articles/PMC4285179/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24122911/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Stat%20Med&title=The%20use%20of%20propensity%20score%20methods%20with%20survival%20or%20time-to-event%20outcomes:%20reporting%20measures%20of%20effect%20similar%20to%20those%20used%20in%20randomized%20experiments&volume=33&issue=7&publication_year=2014&pages=1242-1258&pmid=24122911&doi=10.1002/sim.5984&)]
  * 19.Rubin DB. Multiple Imputation for Nonresponse in Surveys. Wiley; 1987. doi: 10.1002/9780470316696 [[DOI](https://doi.org/10.1002/9780470316696)] [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Multiple%20Imputation%20for%20Nonresponse%20in%20Surveys&publication_year=1987&)]
  * 20.Henry L, Wickham H. rlang: Functions for Base Types and Core R and Tidyverse Features. Published online 2023. Accessed December 10, 2023. <https://CRAN.R-project.org/package=rlang>
  * 21.Richardson N, Cook I, Crane N, et al. arrow: Integration to Apache “Arrow.” Published online 2022. Accessed December 10, 2023. <https://arrow.apache.org/release/4.0.0.html>
  * 22.Wickham H, François R, Henry L, Müller K, Vaughan D. A Grammar of Data Manipulation. Published online 2023. Accessed December 10, 2023. <https://CRAN.R-project.org/package=dplyr>
  * 23.Wickham H, Girlich M. tidyr: Tidy Messy Data. Published online 2022. Accessed December 10, 2023. <https://CRAN.R-project.org/package=tidyr>
  * 24.Spinu V, Grolemund G, Wickham H. lubridate: Make Dealing with Dates a Little Easier. Published online 2023. Accessed December 10, 2023. <https://CRAN.R-project.org/package=lubridate>
  * 25.Wickham H. forcats: Tools for Working with Categorical Variables (Factors). Published online 2021Accessed December 10, 2023. <https://CRAN.R-project.org/package=forcats>
  * 26.Rich B. table1: Tables of Descriptive Statistics in HTML. Published online 2021. Accessed December 10, 2023. <https://github.com/benjaminrich/table1>
  * 27.Greifer N. cobalt: Covariate Balance Tables and Plots. Published online 2023. Accessed December 10, 2023. <https://CRAN.R-project.org/package=cobalt>
  * 28.Ho DE, Imai K, King G, Stuart EA. MatchIt: nonparametric preprocessing for parametric causal inference. J Stat Softw. 2011;42(8):1-28. doi: 10.18637/jss.v042.i08  [[DOI](https://doi.org/10.18637/jss.v042.i08)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Stat%20Softw&title=MatchIt:%20nonparametric%20preprocessing%20for%20parametric%20causal%20inference&volume=42&issue=8&publication_year=2011&pages=1-28&doi=10.18637/jss.v042.i08&)]
  * 29.Greifer N. WeightIt: Weighting for Covariate Balance in Observational Studies. Published online 2023. Accessed December 10, 2023. <https://CRAN.R-project.org/package=WeightIt>
  * 30.van Buuren S, Groothuis-Oudshoorn K. Mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1-67. doi: 10.18637/jss.v045.i03  [[DOI](https://doi.org/10.18637/jss.v045.i03)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Stat%20Softw&title=Mice:%20multivariate%20imputation%20by%20chained%20equations%20in%20R&volume=45&issue=3&publication_year=2011&pages=1-67&doi=10.18637/jss.v045.i03&)]
  * 31.Pishgar F, Greifer N, Leyrat C, Stuart E. MatchThem: matching and weighting after multiple imputation. R J. Published online 2021. doi: 10.32614/RJ-2021-073  [[DOI](https://doi.org/10.32614/RJ-2021-073)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=R%20J&title=MatchThem:%20matching%20and%20weighting%20after%20multiple%20imputation&doi=10.32614/RJ-2021-073&)]
  * 32.Lumley T. survey: analysis of complex survey samples. Published online 2023. Accessed December 10, 2023. <http://r-survey.r-forge.r-project.org/survey/>
  * 33.Therneau TM. Survival: survival analysis. Published online 2023. Accessed December 10, 2023. <https://github.com/therneau/survival>
  * 34.Sjoberg DD, Baillie M, Fruechtenicht C, Haesendonckx S, Treis T. ggsurvfit: Flexible Time-to-Event Figures. Published online 2023. Accessed December 10, 2023. <https://CRAN.R-project.org/package=ggsurvfit>
  * 35.Robinson D, Hayes A, Couch S. broom: Convert Statistical Objects into Tidy Tibbles. Published online 2022. Accessed December 10, 2023. <https://CRAN.R-project.org/package=broom>
  * 36.Wickham H, Chang W, Henry L, et al. ggplot2: Create Elegant Data Visualisations Using the Grammar of Graphics. Published online 2022. Accessed December 10, 2023. <https://CRAN.R-project.org/package=ggplot2>
  * 37.Dahl DB, Scott D, Roosen C, Magnusson A, Swinton J. xtable: Export Tables to LaTeX or HTML. Published online 2019. Accessed December 10, 2023. <http://xtable.r-forge.r-project.org/>
  * 38.A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5). Accessed December 10, 2023. <https://classic.clinicaltrials.gov/ct2/show/NCT05822830>
  * 39.Weiss T, Yang L, Carr RD, et al. Real-world weight change, adherence, and discontinuation among patients with type 2 diabetes initiating glucagon-like peptide-1 receptor agonists in the UK. BMJ Open Diabetes Res Care. 2022;10(1):e002517. doi: 10.1136/bmjdrc-2021-002517  [[DOI](https://doi.org/10.1136/bmjdrc-2021-002517)] [[PMC free article](/articles/PMC8804648/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/35101924/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BMJ%20Open%20Diabetes%20Res%20Care&title=Real-world%20weight%20change,%20adherence,%20and%20discontinuation%20among%20patients%20with%20type%202%20diabetes%20initiating%20glucagon-like%20peptide-1%20receptor%20agonists%20in%20the%20UK&volume=10&issue=1&publication_year=2022&pages=e002517&pmid=35101924&doi=10.1136/bmjdrc-2021-002517&)]
  * 40.Durden E, Liang M, Fowler R, Panton UH, Mocevic E. The Effect of early response to GLP-1 RA therapy on long-term adherence and persistence among type 2 diabetes patients in the United States. J Manag Care Spec Pharm. 2019;25(6):669-680. doi: 10.18553/jmcp.2019.18429  [[DOI](https://doi.org/10.18553/jmcp.2019.18429)] [[PMC free article](/articles/PMC10397904/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/30896359/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Manag%20Care%20Spec%20Pharm&title=The%20Effect%20of%20early%20response%20to%20GLP-1%20RA%20therapy%20on%20long-term%20adherence%20and%20persistence%20among%20type%202%20diabetes%20patients%20in%20the%20United%20States&volume=25&issue=6&publication_year=2019&pages=669-680&pmid=30896359&doi=10.18553/jmcp.2019.18429&)]
  * 41.Wharton S, Astrup A, Endahl L, et al. Estimating and reporting treatment effects in clinical trials for weight management: using estimands to interpret effects of intercurrent events and missing data. Int J Obes (Lond). 2021;45(5):923-933. doi: 10.1038/s41366-020-00733-x  [[DOI](https://doi.org/10.1038/s41366-020-00733-x)] [[PMC free article](/articles/PMC8081661/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/33462358/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Obes%20\(Lond\)&title=Estimating%20and%20reporting%20treatment%20effects%20in%20clinical%20trials%20for%20weight%20management:%20using%20estimands%20to%20interpret%20effects%20of%20intercurrent%20events%20and%20missing%20data&volume=45&issue=5&publication_year=2021&pages=923-933&pmid=33462358&doi=10.1038/s41366-020-00733-x&)]
  * 42.Usman MS, Davies M, Hall ME, et al. The cardiovascular effects of novel weight loss therapies. Eur Heart J. 2023;44(48):5036-5048. doi: 10.1093/eurheartj/ehad664  [[DOI](https://doi.org/10.1093/eurheartj/ehad664)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/37966486/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Heart%20J&title=The%20cardiovascular%20effects%20of%20novel%20weight%20loss%20therapies&volume=44&issue=48&publication_year=2023&pages=5036-5048&pmid=37966486&doi=10.1093/eurheartj/ehad664&)]
  * 43.Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. New England Journal of Medicine. 2023;389(24):2221-2232. doi: 10.1056/NEJMoa2307563  [[DOI](https://doi.org/10.1056/NEJMoa2307563)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/37952131/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=New%20England%20Journal%20of%20Medicine&title=Semaglutide%20and%20cardiovascular%20outcomes%20in%20obesity%20without%20diabetes&volume=389&issue=24&pages=2221-2232&pmid=37952131&doi=10.1056/NEJMoa2307563&)]



## Associated Data

_This section collects any data citations, data availability statements, or supplementary materials included in this article._

### Supplementary Materials

Supplement 1.

eDefinitions

[jamainternmed-e242525-s001.pdf](/articles/instance/11231910/bin/jamainternmed-e242525-s001.pdf) (387.3KB, pdf) 

Supplement 2.

eMethods

eFigure 1. Distribution of initiation time by group

eFigure 2. Distribution of follow-up time by initiation date

eTable 1. Weight Availability at t: On-Treatment Analyses

eTable 2. Weight Availability at t: ITT Analyses

eTable 3. Characteristics of Matched Patients with Available vs. Missing Follow-up Weight.

eResults

eFigure 3. Proportion of at-risk patients achieving weight loss targets by one year for on treatment and intention to treat analyses

eFigure 4. Hazard ratio comparing tirzepatide vs semaglutide for achieving weight loss targets under different analytic approaches

eFigure 5. Mean change in body weight for tirzepatide and semaglutide groups under on treatment and modified intention to treat analyses

eFigure 6. Difference in percent change in body weight comparing tirzepatide to semaglutide under different analytic approaches

eFigure 7. Event probabilities of weight loss, accounting for censoring, for patients on liraglutide and semaglutide

eFigure 8. Hazard ratios comparing liraglutide to semaglutide

eFigure 9. Mean change in body weight for liraglutide and semaglutide

eFigure 10. Difference in percent change in body weight comparing liraglutide to semaglutide

eFigure 11. Weight loss event probabilities, accounting for censoring, for patients with T2D

eFigure 12. Weight loss event probabilities, accounting for censoring, for patients without T2D

eFigure 13. Hazard ratio comparing tirzepatide to semaglutide for different populations

eFigure 14. Difference in percent change in body weight comparing tirzepatide to semaglutide for different populations

eTable 4. Gastrointestinal Adverse Event Rates Per 1000 person-years

[jamainternmed-e242525-s002.pdf](/articles/instance/11231910/bin/jamainternmed-e242525-s002.pdf) (2.2MB, pdf) 

Supplement 3.

Data Sharing Statement

[jamainternmed-e242525-s003.pdf](/articles/instance/11231910/bin/jamainternmed-e242525-s003.pdf) (11KB, pdf) 

* * *

Articles from JAMA Internal Medicine are provided here courtesy of **American Medical Association**

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

## ACTIONS

  * [ View on publisher site ](https://doi.org/10.1001/jamainternmed.2024.2525)
  * 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: http://arxiv.org/abs/2502.17484v1
scrape_date: 2025-02-28T17:23:18.841573
content_type: markdown
hash: a7899d20714b0502ceb822a693be3dc43f2008116c29c102b538d669a6ada81c
title:
[2502.17484v1] Urinary Tract Infection Detection in Digital Remote Monitoring: Strategies for Managing Participant-Specific Prediction Complexity

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:2502.17484v1 

[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 > Signal Processing

**arXiv:2502.17484v1** (eess) 

[Submitted on 18 Feb 2025]

# Title:Urinary Tract Infection Detection in Digital Remote Monitoring: Strategies for Managing Participant-Specific Prediction Complexity

Authors:[Kexin Fan](https://arxiv.org/search/eess?searchtype=author&query=Fan,+K), [Alexander Capstick](https://arxiv.org/search/eess?searchtype=author&query=Capstick,+A), [Ramin Nilforooshan](https://arxiv.org/search/eess?searchtype=author&query=Nilforooshan,+R), [Payam Barnaghi](https://arxiv.org/search/eess?searchtype=author&query=Barnaghi,+P)

View a PDF of the paper titled Urinary Tract Infection Detection in Digital Remote Monitoring: Strategies for Managing Participant-Specific Prediction Complexity, by Kexin Fan and 3 other authors

[View PDF](/pdf/2502.17484v1) [HTML (experimental)](https://arxiv.org/html/2502.17484v1)

> Abstract:Urinary tract infections (UTIs) are a significant health concern, particularly for people living with dementia (PLWD), as they can lead to severe complications if not detected and treated early. This study builds on previous work that utilised machine learning (ML) to detect UTIs in PLWD by analysing in-home activity and physiological data collected through low-cost, passive sensors. The current research focuses on improving the performance of previous models, particularly by refining the Multilayer Perceptron (MLP), to better handle variations in home environments and improve sex fairness in predictions by making use of concepts from multitask learning. This study implemented three primary model designs: feature clustering, loss-dependent clustering, and participant ID embedding which were compared against a baseline MLP model. The results demonstrated that the loss-dependent MLP achieved the most significant improvements, increasing validation precision from 48.92% to 72.60% and sensitivity from 27.44% to 70.52%, while also enhancing model fairness across sexes. These findings suggest that the refined models offer a more reliable and equitable approach to early UTI detection in PLWD, addressing participant-specific data variations and enabling clinicians to detect and screen for UTI risks more effectively, thereby facilitating earlier and more accurate treatment decisions. 

Subjects: |  Signal Processing (eess.SP); Machine Learning (cs.LG)  
---|---  
Cite as: | [arXiv:2502.17484](https://arxiv.org/abs/2502.17484) [eess.SP]  
  | (or  [arXiv:2502.17484v1](https://arxiv.org/abs/2502.17484v1) [eess.SP] for this version)   
  |  <https://doi.org/10.48550/arXiv.2502.17484> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Alexander Capstick [[view email](/show-email/c315100f/2502.17484)]   
**[v1]** Tue, 18 Feb 2025 12:01:55 UTC (2,597 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Urinary Tract Infection Detection in Digital Remote Monitoring: Strategies for Managing Participant-Specific Prediction Complexity, by Kexin Fan and 3 other authors

  * [View PDF](/pdf/2502.17484v1)
  * [HTML (experimental)](https://arxiv.org/html/2502.17484v1)
  * [TeX Source](/src/2502.17484v1)
  * [Other Formats](/format/2502.17484v1)



[ ![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: 

eess.SP

[< prev](/prevnext?id=2502.17484&function=prev&context=eess.SP "previous in eess.SP \(accesskey p\)")   |   [next >](/prevnext?id=2502.17484&function=next&context=eess.SP "next in eess.SP \(accesskey n\)")   


[new](/list/eess.SP/new) |  [recent](/list/eess.SP/recent) | [2025-02](/list/eess.SP/2025-02)

Change to browse by: 

[cs](/abs/2502.17484?context=cs)  
[cs.LG](/abs/2502.17484?context=cs.LG)  
[eess](/abs/2502.17484?context=eess)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2502.17484)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2502.17484)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2502.17484)



[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/2502.17484&description=Urinary Tract Infection Detection in Digital Remote Monitoring: Strategies for Managing Participant-Specific Prediction Complexity "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2502.17484&title=Urinary Tract Infection Detection in Digital Remote Monitoring: Strategies for Managing Participant-Specific Prediction Complexity "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/2502.17484) | [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/2309.02604v1
title: [2309.02604v1] Screening of Pneumonia and Urinary Tract Infection at Triage using TriNet
scrape_date: 2025-02-28T17:23:18.874788
content_type: markdown
hash: 4c12833d21b4ba6d1f583c69f36bacea0e714dacf56b775f0f9ee5d80eb7fa8e
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)](/) > [cs](/list/cs/recent) > arXiv:2309.02604v1 

[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)



# Computer Science > Machine Learning

**arXiv:2309.02604v1** (cs) 

[Submitted on 5 Sep 2023]

# Title:Screening of Pneumonia and Urinary Tract Infection at Triage using TriNet

Authors:[Stephen Z. Lu](https://arxiv.org/search/cs?searchtype=author&query=Lu,+S+Z)

View a PDF of the paper titled Screening of Pneumonia and Urinary Tract Infection at Triage using TriNet, by Stephen Z. Lu

[View PDF](/pdf/2309.02604v1)

> Abstract:Due to the steady rise in population demographics and longevity, emergency department visits are increasing across North America. As more patients visit the emergency department, traditional clinical workflows become overloaded and inefficient, leading to prolonged wait-times and reduced healthcare quality. One of such workflows is the triage medical directive, impeded by limited human workload, inaccurate diagnoses and invasive over-testing. To address this issue, we propose TriNet: a machine learning model for medical directives that automates first-line screening at triage for conditions requiring downstream testing for diagnosis confirmation. To verify screening potential, TriNet was trained on hospital triage data and achieved high positive predictive values in detecting pneumonia (0.86) and urinary tract infection (0.93). These models outperform current clinical benchmarks, indicating that machine-learning medical directives can offer cost-free, non-invasive screening with high specificity for common conditions, reducing the risk of over-testing while increasing emergency department efficiency. 

Comments: | Index Terms: Downstream testing, Machine Learning, Medical directives, Modelling, Modular network, Pneumonia, Positive predictive value, Screening, Triage, Urinary tract infection  
---|---  
Subjects: |  Machine Learning (cs.LG); Computers and Society (cs.CY)  
Cite as: | [arXiv:2309.02604](https://arxiv.org/abs/2309.02604) [cs.LG]  
  | (or  [arXiv:2309.02604v1](https://arxiv.org/abs/2309.02604v1) [cs.LG] for this version)   
  |  <https://doi.org/10.48550/arXiv.2309.02604> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Stephen Lu [[view email](/show-email/87fb122f/2309.02604)]   
**[v1]** Tue, 5 Sep 2023 22:25:30 UTC (939 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Screening of Pneumonia and Urinary Tract Infection at Triage using TriNet, by Stephen Z. Lu

  * [View PDF](/pdf/2309.02604v1)
  * [Other Formats](/format/2309.02604v1)



[ ![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: 

cs.LG

[< prev](/prevnext?id=2309.02604&function=prev&context=cs.LG "previous in cs.LG \(accesskey p\)")   |   [next >](/prevnext?id=2309.02604&function=next&context=cs.LG "next in cs.LG \(accesskey n\)")   


[new](/list/cs.LG/new) |  [recent](/list/cs.LG/recent) | [2023-09](/list/cs.LG/2023-09)

Change to browse by: 

[cs](/abs/2309.02604?context=cs)  
[cs.CY](/abs/2309.02604?context=cs.CY)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2309.02604)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2309.02604)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2309.02604)



[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/2309.02604&description=Screening of Pneumonia and Urinary Tract Infection at Triage using TriNet "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2309.02604&title=Screening of Pneumonia and Urinary Tract Infection at Triage using TriNet "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))_

IArxiv recommender toggle

IArxiv Recommender _([What is IArxiv?](https://iarxiv.org/about))_

  * 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/2309.02604) | [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/1708.01601v1
scrape_date: 2025-02-28T17:23:18.875874
content_type: markdown
hash: 41dd8411ce82bb5a0aca6773aad151dea32038a23dfeb8a6a55e2f9edc9fe5d4
title:
[1708.01601v1] A Clinical and Finite Elements Study of Stress Urinary Incontinence in Women Using Fluid-Structure Interactions

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)](/) > [cs](/list/cs/recent) > arXiv:1708.01601v1 

[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)



# Computer Science > Computational Engineering, Finance, and Science

**arXiv:1708.01601v1** (cs) 

[Submitted on 4 Aug 2017]

# Title:A Clinical and Finite Elements Study of Stress Urinary Incontinence in Women Using Fluid-Structure Interactions

Authors:[Mojtaba Barzegari](https://arxiv.org/search/cs?searchtype=author&query=Barzegari,+M), [Bahman Vahidi](https://arxiv.org/search/cs?searchtype=author&query=Vahidi,+B), [Mohammad Reza Safarinejad](https://arxiv.org/search/cs?searchtype=author&query=Safarinejad,+M+R)

View a PDF of the paper titled A Clinical and Finite Elements Study of Stress Urinary Incontinence in Women Using Fluid-Structure Interactions, by Mojtaba Barzegari and 2 other authors

[View PDF](/pdf/1708.01601v1)

> Abstract:Stress Urinary Incontinence (SUI) or urine leakage from urethra occurs due to an increase in abdominal pressure resulting from stress like a cough or jumping height. SUI is more frequent among post-menopausal women. In the absence of bladder contraction, vesical pressure exceeds from urethral pressure leading to urine leakage. Despite a large number of patients diagnosed with this problem, few studies have investigated its function and mechanics. The main goal of this study is to model bladder and urethra computationally under an external pressure like sneezing. Finite Element Method and Fluid-Structure Interactions are utilized for simulation. Linear mechanical properties assigned to the bladder and urethra and pressure boundary conditions are indispensable in this model. The results show good accordance between the clinical data and predicted values of the computational models, such as the pressure at the center of the bladder. This indicates that numerical methods and simplified physics of biological systems like inferior urinary tract are helpful to achieve the results similar to clinical results, in order to investigate pathological conditions. 

Subjects: |  Computational Engineering, Finance, and Science (cs.CE)  
---|---  
Cite as: | [arXiv:1708.01601](https://arxiv.org/abs/1708.01601) [cs.CE]  
  | (or  [arXiv:1708.01601v1](https://arxiv.org/abs/1708.01601v1) [cs.CE] for this version)   
  |  <https://doi.org/10.48550/arXiv.1708.01601> Focus to learn more arXiv-issued DOI via DataCite  
Related DOI:  | <https://doi.org/10.1007/s11517-020-02148-2> Focus to learn more DOI(s) linking to related resources   
  
## Submission history

From: Mojtaba Barzegari [[view email](/show-email/b7de3cf9/1708.01601)]   
**[v1]** Fri, 4 Aug 2017 17:44:48 UTC (763 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled A Clinical and Finite Elements Study of Stress Urinary Incontinence in Women Using Fluid-Structure Interactions, by Mojtaba Barzegari and 2 other authors

  * [View PDF](/pdf/1708.01601v1)
  * [Other Formats](/format/1708.01601v1)



[view license](http://arxiv.org/licenses/nonexclusive-distrib/1.0/ "Rights to this article")

Current browse context: 

cs.CE

[< prev](/prevnext?id=1708.01601&function=prev&context=cs.CE "previous in cs.CE \(accesskey p\)")   |   [next >](/prevnext?id=1708.01601&function=next&context=cs.CE "next in cs.CE \(accesskey n\)")   


[new](/list/cs.CE/new) |  [recent](/list/cs.CE/recent) | [2017-08](/list/cs.CE/2017-08)

Change to browse by: 

[cs](/abs/1708.01601?context=cs)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:1708.01601)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=1708.01601)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:1708.01601)



### [DBLP](https://dblp.uni-trier.de) \- CS Bibliography

[listing](https://dblp.uni-trier.de/db/journals/corr/corr1708.html#abs-1708-01601 "listing on DBLP") | [bibtex](https://dblp.uni-trier.de/rec/bibtex/journals/corr/abs-1708-01601 "DBLP bibtex record")

[Mojtaba Barzegari](https://dblp.uni-trier.de/search/author?author=Mojtaba%20Barzegari "DBLP author search")  
[Bahman Vahidi](https://dblp.uni-trier.de/search/author?author=Bahman%20Vahidi "DBLP author search")  
[Mohammad Reza Safarinejad](https://dblp.uni-trier.de/search/author?author=Mohammad%20Reza%20Safarinejad "DBLP author search")

[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/1708.01601&description=A Clinical and Finite Elements Study of Stress Urinary Incontinence in Women Using Fluid-Structure Interactions "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/1708.01601&title=A Clinical and Finite Elements Study of Stress Urinary Incontinence in Women Using Fluid-Structure Interactions "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/1708.01601) | [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)



  *[Related DOI]: Digital Object Identifier


url: http://arxiv.org/abs/2111.09414v1
title: [2111.09414v1] Developmental Status and Perspectives for Tissue Engineering in Urology
scrape_date: 2025-02-28T17:23:18.876421
content_type: markdown
hash: fc3437997d11c2f2021830fb609efbd7aff2816147432309039faa3f22c08ff4
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:2111.09414v1 

[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 > Tissues and Organs

**arXiv:2111.09414v1** (q-bio) 

[Submitted on 14 Nov 2021]

# Title:Developmental Status and Perspectives for Tissue Engineering in Urology

Authors:[Elcin Huseyn](https://arxiv.org/search/q-bio?searchtype=author&query=Huseyn,+E)

View a PDF of the paper titled Developmental Status and Perspectives for Tissue Engineering in Urology, by Elcin Huseyn

[View PDF](/pdf/2111.09414v1)

> Abstract:Tissue engineering technology and tissue cell-based stem cell research have made great strides in treating tissue and organ damage, correcting tissue and organ dysfunction, and reducing surgical complications. In the past, traditional methods have used biological substitutes for tissue repair materials, while tissue engineering technology has focused on merging sperm cells with biological materials to form biological tissues with the same structure and function as their own tissues. The advantage is that tissue engineering technology can overcome donors. Material procurement restrictions can effectively reduce complications. The aim of studying tissue engineering technology is to find sperm cells and suitable biological materials to replace the original biological functions of tissues and to establish a suitable in vivo microenvironment. This article mainly describes the current developments of tissue engineering in various fields of urology and discusses the future trends of tissue engineering technology in the treatment of complex diseases of the urinary system. The results of the research in this article indicate that while the current clinical studies are relatively few, the good results from existing animal model studies indicate good prospects of tissue engineering technology for the treatment of various urinary tract diseases in the future. 

Subjects: |  Tissues and Organs (q-bio.TO); Biological Physics (physics.bio-ph)  
---|---  
Cite as: | [arXiv:2111.09414](https://arxiv.org/abs/2111.09414) [q-bio.TO]  
  | (or  [arXiv:2111.09414v1](https://arxiv.org/abs/2111.09414v1) [q-bio.TO] for this version)   
  |  <https://doi.org/10.48550/arXiv.2111.09414> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: Elcin Huseyn [[view email](/show-email/fb6e45a0/2111.09414)]   
**[v1]** Sun, 14 Nov 2021 16:02:02 UTC (241 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Developmental Status and Perspectives for Tissue Engineering in Urology, by Elcin Huseyn

  * [View PDF](/pdf/2111.09414v1)
  * [Other Formats](/format/2111.09414v1)



[ ![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: 

q-bio.TO

[< prev](/prevnext?id=2111.09414&function=prev&context=q-bio.TO "previous in q-bio.TO \(accesskey p\)")   |   [next >](/prevnext?id=2111.09414&function=next&context=q-bio.TO "next in q-bio.TO \(accesskey n\)")   


[new](/list/q-bio.TO/new) |  [recent](/list/q-bio.TO/recent) | [2021-11](/list/q-bio.TO/2021-11)

Change to browse by: 

[physics](/abs/2111.09414?context=physics)  
[physics.bio-ph](/abs/2111.09414?context=physics.bio-ph)  
[q-bio](/abs/2111.09414?context=q-bio)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2111.09414)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2111.09414)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2111.09414)



[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/2111.09414&description=Developmental Status and Perspectives for Tissue Engineering in Urology "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2111.09414&title=Developmental Status and Perspectives for Tissue Engineering in Urology "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/2111.09414) | [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/2312.11355v1
title: [2312.11355v1] Vesicoureteral Reflux Detection with Reliable Probabilistic Outputs
scrape_date: 2025-02-28T17:23:18.876195
content_type: markdown
hash: d460292f3607e138e775880237ebe9f375fd6bb752d3fe1969af3495c7443cf9
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)](/) > [cs](/list/cs/recent) > arXiv:2312.11355v1 

[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)



# Computer Science > Machine Learning

**arXiv:2312.11355v1** (cs) 

[Submitted on 18 Dec 2023]

# Title:Vesicoureteral Reflux Detection with Reliable Probabilistic Outputs

Authors:[Harris Papadopoulos](https://arxiv.org/search/cs?searchtype=author&query=Papadopoulos,+H), [George Anastassopoulos](https://arxiv.org/search/cs?searchtype=author&query=Anastassopoulos,+G)

View a PDF of the paper titled Vesicoureteral Reflux Detection with Reliable Probabilistic Outputs, by Harris Papadopoulos and George Anastassopoulos

[View PDF](/pdf/2312.11355v1) [HTML (experimental)](https://arxiv.org/html/2312.11355v1)

> Abstract:Vesicoureteral Reflux (VUR) is a pediatric disorder in which urine flows backwards from the bladder to the upper urinary tract. Its detection is of great importance as it increases the risk of a Urinary Tract Infection, which can then lead to a kidney infection since bacteria may have direct access to the kidneys. Unfortunately the detection of VUR requires a rather painful medical examination, called voiding cysteourethrogram (VCUG), that exposes the child to radiation. In an effort to avoid the exposure to radiation required by VCUG some recent studies examined the use of machine learning techniques for the detection of VUR based on data that can be obtained without exposing the child to radiation. This work takes one step further by proposing an approach that provides lower and upper bounds for the conditional probability of a given child having VUR. The important property of these bounds is that they are guaranteed (up to statistical fluctuations) to contain well-calibrated probabilities with the only requirement that observations are independent and identically distributed (i.i.d.). Therefore they are much more informative and reliable than the plain yes/no answers provided by other techniques. 

Subjects: |  Machine Learning (cs.LG); Machine Learning (stat.ML)  
---|---  
Cite as: | [arXiv:2312.11355](https://arxiv.org/abs/2312.11355) [cs.LG]  
  | (or  [arXiv:2312.11355v1](https://arxiv.org/abs/2312.11355v1) [cs.LG] for this version)   
  |  <https://doi.org/10.48550/arXiv.2312.11355> Focus to learn more arXiv-issued DOI via DataCite  
Journal reference: | Information Sciences, Volume 308, Pages 113-124, 2015  
Related DOI:  | <https://doi.org/10.1016/j.ins.2014.11.046> Focus to learn more DOI(s) linking to related resources   
  
## Submission history

From: Harris Papadopoulos [[view email](/show-email/9dedb048/2312.11355)]   
**[v1]** Mon, 18 Dec 2023 17:10:10 UTC (57 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Vesicoureteral Reflux Detection with Reliable Probabilistic Outputs, by Harris Papadopoulos and George Anastassopoulos

  * [View PDF](/pdf/2312.11355v1)
  * [HTML (experimental)](https://arxiv.org/html/2312.11355v1)
  * [TeX Source](/src/2312.11355v1)
  * [Other Formats](/format/2312.11355v1)



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

Current browse context: 

cs.LG

[< prev](/prevnext?id=2312.11355&function=prev&context=cs.LG "previous in cs.LG \(accesskey p\)")   |   [next >](/prevnext?id=2312.11355&function=next&context=cs.LG "next in cs.LG \(accesskey n\)")   


[new](/list/cs.LG/new) |  [recent](/list/cs.LG/recent) | [2023-12](/list/cs.LG/2023-12)

Change to browse by: 

[cs](/abs/2312.11355?context=cs)  
[stat](/abs/2312.11355?context=stat)  
[stat.ML](/abs/2312.11355?context=stat.ML)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2312.11355)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2312.11355)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2312.11355)



[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/2312.11355&description=Vesicoureteral Reflux Detection with Reliable Probabilistic Outputs "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2312.11355&title=Vesicoureteral Reflux Detection with Reliable Probabilistic Outputs "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))_

IArxiv recommender toggle

IArxiv Recommender _([What is IArxiv?](https://iarxiv.org/about))_

  * 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/2312.11355) | [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)



  *[Related DOI]: Digital Object Identifier


url: http://arxiv.org/abs/1501.03537v2
scrape_date: 2025-02-28T17:23:18.876186
content_type: markdown
hash: febc6abee07a90669b43c321283ad77e91c2763dd6fdd25737a5c93e8b208973
title:
[1501.03537v2] Variable Selection in Covariate Dependent Random Partition Models: an Application to Urinary Tract Infection

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)](/) > [stat](/list/stat/recent) > arXiv:1501.03537v2 

[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)



# Statistics > Applications

**arXiv:1501.03537v2** (stat) 

[Submitted on 14 Jan 2015 ([v1](https://arxiv.org/abs/1501.03537v1)), last revised 10 Jul 2015 (this version, v2)]

# Title:Variable Selection in Covariate Dependent Random Partition Models: an Application to Urinary Tract Infection

Authors:[William Barcella](https://arxiv.org/search/stat?searchtype=author&query=Barcella,+W), [Maria De Iorio](https://arxiv.org/search/stat?searchtype=author&query=De+Iorio,+M), [Gianluca Baio](https://arxiv.org/search/stat?searchtype=author&query=Baio,+G), [James Malone-Lee](https://arxiv.org/search/stat?searchtype=author&query=Malone-Lee,+J)

View a PDF of the paper titled Variable Selection in Covariate Dependent Random Partition Models: an Application to Urinary Tract Infection, by William Barcella and 2 other authors

[View PDF](/pdf/1501.03537v2)

> Abstract:Lower urinary tract symptoms (LUTS) can indicate the presence of urinary tract infection (UTI), a condition that if it becomes chronic requires expensive and time consuming care as well as leading to reduced quality of life. Detecting the presence and gravity of an infection from the earliest symptoms is then highly valuable. Typically, white blood cell count (WBC) measured in a sample of urine is used to assess UTI. We consider clinical data from 1341 patients at their first visit in which UTI (i.e. WBC$\geq 1$) is diagnosed. In addition, for each patient, a clinical profile of 34 symptoms was recorded. In this paper we propose a Bayesian nonparametric regression model based on the Dirichlet Process (DP) prior aimed at providing the clinicians with a meaningful clustering of the patients based on both the WBC (response variable) and possible patterns within the symptoms profiles (covariates). This is achieved by assuming a probability model for the symptoms as well as for the response variable. To identify the symptoms most associated to UTI, we specify a spike and slab base measure for the regression coefficients: this induces dependence of symptoms selection on cluster assignment. Posterior inference is performed through Markov Chain Monte Carlo methods. 

Comments: | Revised version. 24 pages, 6 figures  
---|---  
Subjects: |  Applications (stat.AP)  
Cite as: | [arXiv:1501.03537](https://arxiv.org/abs/1501.03537) [stat.AP]  
  | (or  [arXiv:1501.03537v2](https://arxiv.org/abs/1501.03537v2) [stat.AP] for this version)   
  |  <https://doi.org/10.48550/arXiv.1501.03537> Focus to learn more arXiv-issued DOI via DataCite  
  
## Submission history

From: William Barcella [[view email](/show-email/76a151ff/1501.03537)]   
**[[v1]](/abs/1501.03537v1)** Wed, 14 Jan 2015 23:47:46 UTC (106 KB)  
**[v2]** Fri, 10 Jul 2015 09:43:31 UTC (97 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Variable Selection in Covariate Dependent Random Partition Models: an Application to Urinary Tract Infection, by William Barcella and 2 other authors

  * [View PDF](/pdf/1501.03537v2)
  * [TeX Source](/src/1501.03537v2)
  * [Other Formats](/format/1501.03537v2)



[view license](http://arxiv.org/licenses/nonexclusive-distrib/1.0/ "Rights to this article")

Current browse context: 

stat.AP

[< prev](/prevnext?id=1501.03537&function=prev&context=stat.AP "previous in stat.AP \(accesskey p\)")   |   [next >](/prevnext?id=1501.03537&function=next&context=stat.AP "next in stat.AP \(accesskey n\)")   


[new](/list/stat.AP/new) |  [recent](/list/stat.AP/recent) | [2015-01](/list/stat.AP/2015-01)

Change to browse by: 

[stat](/abs/1501.03537?context=stat)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:1501.03537)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=1501.03537)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:1501.03537)



[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/1501.03537&description=Variable Selection in Covariate Dependent Random Partition Models: an Application to Urinary Tract Infection "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/1501.03537&title=Variable Selection in Covariate Dependent Random Partition Models: an Application to Urinary Tract Infection "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/1501.03537) | [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/2402.09498v1
scrape_date: 2025-02-28T17:23:18.876175
content_type: markdown
hash: eb60cf32ca8649db7a1206fd11703ca5094505754aede346e59d2c6f2e1af805
title:
[2402.09498v1] Detection of the most influential variables for preventing postpartum urinary incontinence using machine learning techniques

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)](/) > [cs](/list/cs/recent) > arXiv:2402.09498v1 

[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)



# Computer Science > Artificial Intelligence

**arXiv:2402.09498v1** (cs) 

[Submitted on 14 Feb 2024]

# Title:Detection of the most influential variables for preventing postpartum urinary incontinence using machine learning techniques

Authors:[José Alberto Benítez-Andrades](https://arxiv.org/search/cs?searchtype=author&query=Ben%C3%ADtez-Andrades,+J+A), [María Teresa García-Ordás](https://arxiv.org/search/cs?searchtype=author&query=Garc%C3%ADa-Ord%C3%A1s,+M+T), [María Álvarez-González](https://arxiv.org/search/cs?searchtype=author&query=%C3%81lvarez-Gonz%C3%A1lez,+M), [Raquel Leirós-Rodríguez](https://arxiv.org/search/cs?searchtype=author&query=Leir%C3%B3s-Rodr%C3%ADguez,+R), [Ana F López Rodríguez](https://arxiv.org/search/cs?searchtype=author&query=Rodr%C3%ADguez,+A+F+L)

View a PDF of the paper titled Detection of the most influential variables for preventing postpartum urinary incontinence using machine learning techniques, by Jos\'e Alberto Ben\'itez-Andrades and 3 other authors

[View PDF](/pdf/2402.09498v1)

> Abstract:Background: Postpartum urinary incontinence (PUI) is a common issue among postnatal women. Previous studies identified potential related variables, but lacked analysis on certain intrinsic and extrinsic patient variables during pregnancy.   
> Objective: The study aims to evaluate the most influential variables in PUI using machine learning, focusing on intrinsic, extrinsic, and combined variable groups.   
> Methods: Data from 93 pregnant women were analyzed using machine learning and oversampling techniques. Four key variables were predicted: occurrence, frequency, intensity of urinary incontinence, and stress urinary incontinence.   
> Results: Models using extrinsic variables were most accurate, with 70% accuracy for urinary incontinence, 77% for frequency, 71% for intensity, and 93% for stress urinary incontinence.   
> Conclusions: The study highlights extrinsic variables as significant predictors of PUI issues. This suggests that PUI prevention might be achievable through healthy habits during pregnancy, although further research is needed for confirmation. 

Subjects: |  Artificial Intelligence (cs.AI)  
---|---  
Cite as: | [arXiv:2402.09498](https://arxiv.org/abs/2402.09498) [cs.AI]  
  | (or  [arXiv:2402.09498v1](https://arxiv.org/abs/2402.09498v1) [cs.AI] for this version)   
  |  <https://doi.org/10.48550/arXiv.2402.09498> Focus to learn more arXiv-issued DOI via DataCite  
Journal reference: | Digital Health, Volume 8, 2022, 20552076221111289  
Related DOI:  | <https://doi.org/10.1177/20552076221111289> Focus to learn more DOI(s) linking to related resources   
  
## Submission history

From: José Alberto Benítez-Andrades Ph.D. [[view email](/show-email/45181a5e/2402.09498)]   
**[v1]** Wed, 14 Feb 2024 16:45:10 UTC (1,811 KB)  


Full-text links:

## Access Paper:

View a PDF of the paper titled Detection of the most influential variables for preventing postpartum urinary incontinence using machine learning techniques, by Jos\'e Alberto Ben\'itez-Andrades and 3 other authors

  * [View PDF](/pdf/2402.09498v1)
  * [Other Formats](/format/2402.09498v1)



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

Current browse context: 

cs.AI

[< prev](/prevnext?id=2402.09498&function=prev&context=cs.AI "previous in cs.AI \(accesskey p\)")   |   [next >](/prevnext?id=2402.09498&function=next&context=cs.AI "next in cs.AI \(accesskey n\)")   


[new](/list/cs.AI/new) |  [recent](/list/cs.AI/recent) | [2024-02](/list/cs.AI/2024-02)

Change to browse by: 

[cs](/abs/2402.09498?context=cs)  


### References & Citations

  * [NASA ADS](https://ui.adsabs.harvard.edu/abs/arXiv:2402.09498)
  * [Google Scholar](https://scholar.google.com/scholar_lookup?arxiv_id=2402.09498)
  * [Semantic Scholar](https://api.semanticscholar.org/arXiv:2402.09498)



[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/2402.09498&description=Detection of the most influential variables for preventing postpartum urinary incontinence using machine learning techniques "Bookmark on BibSonomy") [ ![Reddit logo](/static/browse/0.3.4/images/icons/social/reddit.png) ](https://reddit.com/submit?url=https://arxiv.org/abs/2402.09498&title=Detection of the most influential variables for preventing postpartum urinary incontinence using machine learning techniques "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/2402.09498) | [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)



  *[Related DOI]: Digital Object Identifier


url: https://pmc.ncbi.nlm.nih.gov/articles/PMC4549700/
scrape_date: 2025-02-28T17:23:19.087215
content_type: markdown
hash: d37c488848eb2e593a881b62400fb81bf49e4ffb8139e064eda2e674ecf46fac
title:
            Tadalafil for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a review of clinical data in Asian men and an update on the mechanism of action - 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/10.1177/1756287215589238 "View on publisher site")
  * [ ](pdf/10.1177_1756287215589238.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/)

![Therapeutic Advances in Urology logo](https://cdn.ncbi.nlm.nih.gov/pmc/banners/logo-tau.png)

Ther Adv Urol

. 2015 Oct;7(5):249–264. doi: [10.1177/1756287215589238](https://doi.org/10.1177/1756287215589238)

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



# Tadalafil for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a review of clinical data in Asian men and an update on the mechanism of action

[Osamu Yokoyama](https://pubmed.ncbi.nlm.nih.gov/?term=%22Yokoyama%20O%22%5BAuthor%5D)

### Osamu Yokoyama

1Department of Urology, Faculty of Medical Science, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan

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

1,✉, [Yasuhiko Igawa](https://pubmed.ncbi.nlm.nih.gov/?term=%22Igawa%20Y%22%5BAuthor%5D)

### Yasuhiko Igawa

2Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

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

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

### Masayuki Takeda

3Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan

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

3, [Takafumi Yamaguchi](https://pubmed.ncbi.nlm.nih.gov/?term=%22Yamaguchi%20T%22%5BAuthor%5D)

### Takafumi Yamaguchi

4Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Hyogo, Japan

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

4, [Masahiro Murakami](https://pubmed.ncbi.nlm.nih.gov/?term=%22Murakami%20M%22%5BAuthor%5D)

### Masahiro Murakami

5Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Hyogo, Japan

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

5, [Lars Viktrup](https://pubmed.ncbi.nlm.nih.gov/?term=%22Viktrup%20L%22%5BAuthor%5D)

### Lars Viktrup

6Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana, USA

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

6

  * Author information
  * Article notes
  * Copyright and License information



1Department of Urology, Faculty of Medical Science, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan

2Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

3Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan

4Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Hyogo, Japan

5Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Hyogo, Japan

6Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana, USA

✉

Email: oyoko@u-fukui.ac.jp

✉

Corresponding author.

Issue date 2015 Oct.

© The Author(s), 2015

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

PMCID: PMC4549700 PMID: [26425140](https://pubmed.ncbi.nlm.nih.gov/26425140/)

## Abstract

Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, is approved worldwide for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS). The purpose of this narrative review is to summarize the clinical data on tadalafil 5 mg once-daily, primarily focusing on Asian men with BPH-LUTS, and to update the current understanding of the mechanism of action underlying PDE5 inhibition. Findings from studies have demonstrated that PDE5 is highly expressed in the lower urinary tract and supporting vasculature, and that PDE5 inhibition potentially decreases smooth muscle cell proliferation in the prostate, relaxes smooth muscle in the prostate, bladder neck and supporting vasculature, increases blood perfusion to the lower urinary tract, and modulates bladder afferent nerve activity. A total of 11 larger, 12-week, double-blind, randomized, placebo-controlled studies of tadalafil, including four Asian studies, have been conducted globally, enrolling >3000 men with BPH-LUTS. In addition, two long-term (42- and 52-week) studies enrolled 394 Japanese and 428 North American men, respectively, with BPH-LUTS. Overall, tadalafil 5 mg once-daily resulted in significant improvements in the change from baseline to endpoint in total International Prostate Symptom Scores (IPSS), IPSS storage and voiding subscores, and IPSS quality of life index compared with placebo. Tadalafil was well tolerated and had a favorable safety profile. These findings support tadalafil 5 mg once-daily for treating men, including Asian men, with BPH-LUTS.

**Keywords:** Asia, benign prostatic hyperplasia, lower urinary tract symptoms, mechanism of action, tadalafil

## Introduction

Benign prostatic hyperplasia (BPH) is a histological diagnosis characterized by nonmalignant hyperplasia of prostatic tissue that is caused by smooth muscle and epithelial cell proliferation in the prostate transition zone [Roehrborn, 2008; Oelke _et al._ 2013]. This hyperplasia results in prostate enlargement [Roehrborn, 2008; Oelke _et al._ 2013], which can in turn lead to the development of lower urinary tract symptoms (LUTS) such as storage, voiding and postmicturition symptoms [Abrams _et al._ 2003; Homma _et al._ 2011]. An increased smooth muscle tone in the prostate or the vasculature supporting the lower urinary tract may play a contributing role [Homma _et al._ 2011]. LUTS secondary to BPH (BPH-LUTS) are common in aging men worldwide [Verhamme _et al._ 2002; Irwin _et al._ 2006; Coyne _et al._ 2009], including Asia [Tsukamoto _et al._ 1995; Lee _et al._ 1998; Li _et al._ 2005; Kang _et al._ 2011]. In the US, approximately 75% of men aged 60–69 years and 83% of men aged 70 years or older are estimated to have BPH-LUTS [Wei _et al._ 2008]. In Japan, an estimated 1.98 million men were projected to require treatment for BPH-LUTS in 2010, a number that is expected to increase to 2.19 million by 2030 [Terai _et al._ 2000]. Given that BPH-LUTS often interferes with activities of daily living [Rosen _et al._ 2003], many men with BPH-LUTS seek treatment to improve their quality of life (QoL) [Jacobsen _et al._ 1993].

Pharmacological treatment for men with BPH-LUTS typically begins with an α-adrenergic blocker (α-blocker), with the addition of a 5-α-reductase inhibitor (5ARI) in men with verified prostate enlargement. Of these treatments, α-blockers may reduce LUTS within weeks, whereas 5ARIs have a slower onset of action (within 6–12 months) [Homma _et al._ 2011; Oelke _et al._ 2013]. Long-term treatment with 5ARIs may also reduce the risk of urinary retention and surgical intervention [American Urological Association Practice Guidelines Committee, 2010; Oelke _et al._ 2013]. Although these treatments may be effective, individually or in combination, some men do not respond or experience side effects such as sexual dysfunction, including ejaculatory disorders (α-blockers and 5ARIs), orthostatic hypotension (α-blockers) and intraoperative floppy iris syndrome during cataract surgery (α-blockers) [Homma _et al._ 2011]. Further, persistent adverse effects on sexual function, including erectile dysfunction (ED) and decreased libido, have been reported in a subset of patients with BPH-LUTS treated with 5ARIs [Traish _et al._ 2011].

Recently, the phosphodiesterase type 5 (PDE5) inhibitor tadalafil, widely approved as once-daily and/or on-demand treatment for ED, has been approved (5 mg once-daily) for the treatment of BPH-LUTS worldwide, including in several Asian countries, the US and the European Union. Like α-blockers, tadalafil has an onset of action that occurs within weeks [Egerdie _et al._ 2012; Oelke _et al._ 2012; Yokoyama _et al._ 2013]. The efficacy of PDE5 inhibitors, with a focus on tadalafil clinical data, was acknowledged in the recent guidelines published by the Japanese Urological Association (JUA) [Homma _et al._ 2011] and the European Association of Urology (EAU) [Oelke _et al._ 2013], both of which state that there is Level 1 evidence (i.e. from multiple, large-scale, randomized, controlled trials, the majority involving tadalafil) supporting the efficacy of PDE5 inhibitors for the treatment of BPH-LUTS.

The purpose of this narrative review, focusing on Asian men with BPH-LUTS, is to summarize the clinical data on tadalafil 5 mg once-daily as monotherapy or in combination with α-blockers or 5ARIs, and to update the current understanding of the mechanism of action underlying PDE5 inhibition. The review of clinical data was focused on published findings from key randomized, placebo-controlled studies examining the efficacy of tadalafil 5 mg once-daily in men (_n_ ⩾ 50 in the tadalafil treatment arm) with BPH-LUTS.

## Potential pathology

Pathophysiological changes underlying the development of BPH-LUTS are multifaceted and may include reduced pelvic nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling, overactivity of the autonomic nervous system, atherosclerosis, pelvic ischemia, increased Rho-kinase activity (which mediates smooth muscle contraction by modulating the activity of myosin phosphatase), an altered androgen environment and tissue inflammation [Andersson _et al._ 2011]. These changes may mediate increased smooth muscle cell (SMC) proliferation, SMC tone and bladder afferent nerve activity [Andersson _et al._ 2011; Giuliano _et al._ 2013]. The resultant structural and functional changes in the bladder, prostate, supporting vasculature and nerve innervation can affect bladder function [Andersson _et al._ 2011]. Metabolic syndrome may be independently associated with BPH-LUTS [Moul and McVary, 2010]. Although a direct causal link has not been identified, several of the characteristic changes associated with metabolic syndrome, including insulin resistance, hormonal changes, pelvic atherosclerosis and inflammation, seem to contribute to the development of LUTS [De Nunzio _et al._ 2012]. The results of a recently published systematic review and meta-analysis have also demonstrated a link between metabolic syndrome, in particular dyslipidemia and central obesity, and prostate enlargement [Gacci _et al._ 2015].

## Location of PDE5 isoenzymes

To date, PDE5 isoenzymes have been identified in the SMCs of the corpus cavernosum [Taher _et al._ 1997], vascular and visceral smooth muscle [Rybalkin _et al._ 1999; Watkins _et al._ 2000], skeletal muscle [Loughney _et al._ 1998], platelets [Haslam _et al._ 1999], kidney [Kotera _et al._ 2000], lung [Cortijo _et al._ 1998], spinal cord [Fullhase _et al._ 2013], cerebellum [Kotera _et al._ 2000] and pancreas [Loughney _et al._ 1998]. In the lower urinary tract, PDE5 isoenzymes have been identified in the prostate [Uckert _et al._ 2001; Filippi _et al._ 2007; Waldkirch _et al._ 2007; Fibbi _et al._ 2010; Morelli _et al._ 2011a], urethra [Werkstrom _et al._ 2006; Fibbi _et al._ 2010; Morelli _et al._ 2011a] and bladder [Filippi _et al._ 2007; Fibbi _et al._ 2010; Morelli _et al._ 2011a] (Figure 1).

### Figure 1.

[![Figure 1.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/369a/4549700/012ee30871d8/10.1177_1756287215589238-fig1.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=4549700_10.1177_1756287215589238-fig1.jpg)

[Open in a new tab](figure/fig1-1756287215589238/)

Location of phosphodiesterase type 5 (PDE5) isoenzymes in the lower urinary tract.

Note: This figure was originally published in _Eur Urol_ 2013; 63: 506–516.

## PDE5 inhibition

In NO/cGMP signaling, PDE5 isoenzymes catalyze cGMP hydrolysis, thereby regulating the activity of cGMP-dependent protein kinases (PKGs) [Francis _et al._ 2010]. The proteins modified by PKGs play a role in regulating cellular calcium homeostasis [Francis _et al._ 2010]. The inhibition of PDE5 in SMCs potentiates the action of NO by increasing cGMP concentrations which, in turn, lead to calcium efflux and SMC relaxation. The inhibition of PDE5 isoenzymes in the lower urinary tract mediates a number of processes that may help relieve BPH-LUTS.

### Smooth muscle relaxation

Organ bath studies of human prostate and bladder tissue have shown that PDE5 inhibitors induce smooth muscle relaxation. Specifically, a study of human prostate tissue, obtained from patients with BPH who underwent suprapubic adenectomy or from organ donors free from urologic disease, demonstrated that tadalafil potentiated sodium nitroprusside (SNP) induced relaxation in muscle strips and enhanced cGMP accumulation in homogenized tissue [Angulo _et al._ 2012]. Other studies demonstrated that PDE5 inhibitors attenuated α-adrenergic-induced contractions [Uckert _et al._ 2001; Uckert _et al._ 2008], including in a concentration-dependent manner [Uckert _et al._ 2008], or electrical field-induced contractions [Takeda _et al._ 1995] in isolated human prostate strips obtained from nonmalignant tissue from men who had undergone surgery for localized prostate or urinary bladder cancer. Studies have also demonstrated that vardenafil potentiated SNP-induced relaxation [Filippi _et al._ 2007],and that sildenafil citrate induced relaxation [Bittencourt _et al._ 2009], of precontracted human bladder neck strips obtained from men undergoing transvesical prostate adenectomy, radical cystectomy or radical prostatectomy.

### Increased blood perfusion

Animal and human studies have shown that PDE5 inhibitors can increase prostate and/or bladder blood perfusion. In spontaneously hypertensive rats (SHR), which exhibit prostate hyperplasia, bladder overactivity, and an increased density of hypoxic cells in prostate and bladder tissue, 7 days of tadalafil administration normalized the density of hypoxic cells in prostate tissue slices [Morelli _et al._ 2011a]. Likewise, in a similar SHR study, vardenafil, administered 90 minutes before sacrifice, normalized the density of hypoxic cells in bladder tissue slices [Morelli _et al._ 2010]. In a clinical study, an increase in prostate microcirculation was demonstrated, using power Doppler ultrasound, 60 minutes after vardenafil 20 mg administration in men (_n_ = 9) who were prostate biopsy naïve and had a prostate-specific antigen concentration >4 ng/ml at first diagnosis with negative digital rectal and transrectal ultrasound examinations [Morelli _et al._ 2011b]. In another study, an increase in prostate blood flow was demonstrated, using transrectal contrast-enhanced ultrasound, 90 minutes after tadalafil 20 mg administration in men (_n_ = 12) with BPH awaiting benign prostate surgery [Bertolotto _et al._ 2009]. Furthermore, in a case report of a man with a normal prostate, an approximate 75% increase in prostate blood flow was detected using dynamic contrast enhanced magnetic resonance imaging 60 minutes after administration of sildenafil citrate 25 mg [Haaga _et al._ 2007].

Encouraged by these results, a double-blind, randomized, placebo-controlled study of 97 men with BPH-LUTS was carried out to assess the arterial resistive index in the prostate transition zone and other flow measures in the prostate peripheral zone and bladder neck _via_ transrectal ultrasonography after 8 weeks of tadalafil 5 mg once-daily therapy compared with placebo [Pinggera _et al._ 2014]. However, no detectable improvements were observed across several parameters. One potential explanation for the lack of improvement is that the prostatic arterial resistive index observed at baseline was less severe than reported in previous studies [Kojima _et al._ 1997; Tsuru _et al._ 2002; Berger _et al._ 2005; Ozden _et al._ 2010; Abdelwahab _et al._ 2012; Zhang _et al._ 2012], leaving less room for improvement. Other explanations include potential insufficient sensitivity of the novel techniques used, methodological variability across study sites, or PDE5 inhibition having an inconsistent impact on prostate blood perfusion [Pinggera _et al._ 2014].

Inhibition of PDE5 may also affect vascular reactivity _via_ mediators of endothelial function. Specifically, sildenafil citrate has been demonstrated to enhance epithelial NO synthase (eNOS) expression in the sickle cell mouse penis [Musicki _et al._ 2014] and to restore eNOS activation in human umbilical vein endothelial cells cultured under conditions designed to mimic insulin resistance [Mammi _et al._ 2011]. Moreover, a study of 32 men with increased cardiovascular risk demonstrated that 4 weeks of treatment with tadalafil 20 mg resulted in improved brachial artery flow-mediated dilation and decreased plasma concentrations of endothelin-1, a vasoconstrictor produced by the vascular endothelium [Rosano _et al._ 2005].

### Decreased afferent nerve activity

Animal studies involving models of bladder distension, spinal cord injury and bladder outlet obstruction have shown that PDE5 inhibition modulates bladder afferent nerve activity. Specifically, tadalafil significantly decreased the single bladder afferent (afferents were identified by electrical stimulation of the pelvic nerve and bladder distension) activity of both Aδ- and C-fibers induced by bladder distension or acrolein instillation in rats [Minagawa _et al._ 2012]. In another study, vardenafil decreased both bladder afferent (afferents were identified as described above) nerve firing during filling and the amplitude of nonvoiding contractions in rats with spinal cord injury [Behr-Roussel _et al._ 2011]. In a study of bladder outlet obstruction through partial urethral ligation in rats, vardenafil decreased nonvoiding contractions [Filippi _et al._ 2007].

In addition to the effects on afferent nerves in the bladder, a study of bladder overactivity _via_ partial urethral obstruction in rats demonstrated that intrathecal sildenafil citrate administered at the level of the sacral spinal cord decreased both the frequency of micturition and bladder pressure [Fullhase _et al._ 2013].

### Decreased SMC proliferation

The findings from several _in vitro_ studies indicate that PDE5 inhibitors exert antiproliferative effects on human SMCs. Specifically, in a study of human prostatic SMCs obtained from men with BPH, PDE5 inhibition was demonstrated to inhibit lysophosphatidic acid induced increases in DNA replication by nearly 100% [Adolfsson _et al._ 2002]. More recently, a study of human bladder, prostatic and urethral SMCs, obtained from men who underwent suprapubic adenectomy for BPH, demonstrated that vardenafil significantly increased the antiproliferative effect (determined by cell counting) of the NO donor SNP [Fibbi _et al._ 2010].

In addition to these effects on SMCs, a study of human prostatic stromal cells demonstrated that vardenafil significantly attenuated transforming growth factor β1-induced fibroblast-to-myofibroblast transdifferentiation (determined by assessing SMC actin and insulin-like growth factor binding protein 3 mRNA and protein levels), an important underlying change in BPH [Zenzmaier _et al._ 2012]. Furthermore, the fibroblast-like morphology in transdifferentiated myofibroblasts was restored [Zenzmaier _et al._ 2012].

### Summary

Several different pathophysiological changes in the bladder, prostate, supporting vasculature and nerve supply may lead to LUTS in men with BPH. The abundance of PDE5 isoenzymes in the lower urinary tract and the inhibition of PDE5 in these tissues, leading to increased cGMP, have been demonstrated to reduce SMC proliferation, relax SMCs, increase tissue oxygenation and modulate afferent nerve activity. The improvement of symptoms in patients with BPH-LUTS treated with tadalafil is most likely mediated by a combination of these effects.

## Clinical efficacy and safety data

More than 3000 men with BPH-LUTS have participated in 11 large, randomized, placebo-controlled studies of tadalafil carried out globally [McVary _et al._ 2007; Roehrborn _et al._ 2008; Dmochowski _et al._ 2010; Kim _et al._ 2011; Porst _et al._ 2011; Egerdie _et al._ 2012; Goldfischer _et al._ 2012; Oelke _et al._ 2012; Takeda _et al._ 2012, 2014; Yokoyama _et al._ 2013]. Two long-term, open-label studies enrolled 394 Japanese [Takeda _et al._ 2012] and 428 North American [Donatucci _et al._ 2011] men. In addition, two large, randomized, placebo-controlled studies of tadalafil combination therapy with finasteride [Casabe _et al._ 2014] or α-blockers [Goldfischer _et al._ 2012] enrolled 346 and 158 men, respectively. Studies enrolling fewer than 50 patients to the tadalafil treatment arm are not included in this review.

### Efficacy

To date, three 12-week, randomized, controlled studies [Takeda _et al_. 2012; Yokoyama _et al._ 2013; Takeda _et al._ 2014], a 12-week, randomized, controlled pilot study [Kim _et al._ 2011], and a 42-week, open-label, extension study [Takeda _et al_. 2012] have investigated the efficacy of tadalafil 5 mg once-daily as a treatment for BPH-LUTS in men from Asian countries. Four 12-week, randomized, controlled studies [Roehrborn _et al._ 2008; Porst _et al._ 2011; Egerdie _et al._ 2012; Oelke _et al._ 2012] and a 1-year, open-label, extension study [Donatucci _et al._ 2011] have investigated the efficacy of tadalafil 5 mg once-daily in men from non-Asian countries. These studies included men aged ⩾45 years with a 6-month history of BPH-LUTS, a total International Prostate Symptom Score (IPSS) ⩾13 and intermediate voiding obstruction as defined by maximum urinary flow (Qmax) of 4–15 ml/s. In all of these studies, the primary or coprimary outcome was the change from baseline to endpoint in total IPSS for tadalafil 5 mg compared with placebo. The IPSS [Barry _et al._ 1992; Homma _et al._ 2002] is widely accepted and recommended as the standard instrument for assessing BPH-LUTS worldwide [Homma _et al._ 2011; Oelke _et al._ 2013].

#### Asian studies

The 12-week, double-blind, randomized, placebo-controlled studies of tadalafil 5 mg once-daily in Japanese men [Takeda _et al._ 2012], Japanese, Korean and Taiwanese men [Yokoyama _et al._ 2013], and Japanese and Korean men [Takeda _et al._ 2014] consistently demonstrated greater improvement in the change from baseline to endpoint in total IPSS for tadalafil 5 mg compared with placebo (Figure 2A). The improvement was significantly greater (_p_ < 0.05) in two of these studies [Yokoyama _et al._ 2013; Takeda _et al._ 2014], whereas in the third smaller study [Takeda _et al._ 2012], the magnitude of symptom improvement (IPSS) was numerically greater (_p_ = 0.062) on primary analysis (analysis of covariance) and significantly greater (_p_ < 0.05) on secondary analysis (mixed-effects models repeated measures). Of note, integrated analysis of data from these three studies demonstrated significantly greater improvement in total IPSS for tadalafil 5 mg compared with placebo (mean change from baseline to endpoint: placebo = −3.8, tadalafil = −5.3; _p_ < 0.001 [Nishizawa _et al_. 2015]).

##### Figure 2.

[![Figure 2.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/369a/4549700/bce49e8fa8d0/10.1177_1756287215589238-fig2.jpg)](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=4549700_10.1177_1756287215589238-fig2.jpg)

[Open in a new tab](figure/fig2-1756287215589238/)

Change from baseline to endpoint in total IPSS after 12 weeks of treatment with placebo or tadalafil 5 mg in (A) Asian and (B) non-Asian randomized, controlled studies of men with lower urinary tract symptoms secondary to benign prostatic hyperplasia; _p_ values represent the tadalafil _versus_ placebo comparison in each study.

aFull study.

bPilot study.

IPSS, International Prostate Symptom Score; _n_ = number of randomized participants.

The randomized, controlled Asian studies also consistently demonstrated greater improvement in secondary efficacy measures, including the change from baseline to endpoint in IPSS storage and voiding subscores and IPSS QoL index, for tadalafil 5 mg compared with placebo (Table 1). The magnitude of improvement in the IPSS storage subscore was significantly greater (_p_ < 0.05) in two studies [Yokoyama _et al._ 2013; Takeda _et al._ 2014] and numerically greater in one study [Takeda _et al._ 2012], whereas the magnitude of improvement in the IPSS voiding subscore and IPSS QoL index was significantly greater (_p_ < 0.05) in all three studies [Takeda _et al._ 2012, 2014; Yokoyama _et al._ 2013].

##### Table 1.

Mean changes from baseline to endpoint in IPSS storage and voiding subscores, IPSS quality of life index, and maximum urinary flow rate in 12-week, double-blind, randomized, placebo-controlled clinical studies of tadalafil 5 mg in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Study | Treatment | _n_ | Mean change from baseline

* * *  
  
---|---|---|---  
|  |  | IPSS storage subscore | IPSS voiding subscore | IPSS QoL index | Qmax, ml/s  
Asian studies  
Takeda _et al._ [2014 ] | Placebo | 304 | −1.4 | −3.1 | −0.9 | 0.6‡  
| Tadalafil | 306 | −2.0* | −4.0* | −1.1* | 1.2‡  
Yokoyama _et al._ [2013]$ | Placebo | 154 | −1.1 | −1.9 | −0.5 | 2.1  
| Tadalafil | 155 | −1.7* | −3.0* | −0.8* | 1.3  
Takeda _et al._ [2012]$ | Placebo | 140 | −1.4 | −2.4 | −0.4 | 1.4  
| Tadalafil | 140 | −1.6 | −3.3* | −0.7* | 0.6  
Kim _et al._ [2011] | Placebo | 51 | −1.5 | −2.7 | −0.9 | 2.3  
| Tadalafil | 51 | −2.1 | −3.7 | −1.2 | 2.5  
Non-Asian studies  
Roehrborn _et al._ [2008]§ | Placebo | 210 | −1.0 | −1.3 | −0.5 | 1.2  
| Tadalafil | 212 | −1.9* | −2.9* | −0.9* | 1.6  
Egerdie _et al._ [2012]$ | Placebo | 200 | −1.6 | −2.2 | −0.8 | 1.2  
| Tadalafil | 208 | −2.5* | −3.6* | −1.0 | 1.7  
Oelke _et al._ [2012] | Placebo | 172 | −1.6 | −2.6 | −1.0 | 1.2  
| Tadalafil | 171 | −2.2 | −4.1* | −1.3* | 2.4*  
Porst _et al._ [2011] | Placebo | 164 | −1.3 | −2.3 | −0.7 | 1.1  
| Tadalafil | 161 | −2.3* | −3.3* | −1.0* | 1.6  
  
[Open in a new tab](table/table1-1756287215589238/)

*

_p_ < 0.05 _versus_ placebo

$

Tadalafil 2.5 mg was also tested in this study.

‡

Median change from baseline to endpoint.

§

Tadalafil 2.5, 10., and 20 mg were also tested in this study.

IPSS = International Prostate Symptom Score; _n_ = number of randomized participants; Qmax = maximum urinary flow rate; QoL = quality of life.

In the two randomized, controlled Asian studies in which assessments were made [Yokoyama _et al._ 2013; Takeda _et al._ 2014], a greater proportion of participants treated with tadalafil had better or improved urinary symptoms compared with those treated with placebo, as assessed by both the Patient and Clinician Global Impression of Improvement instruments.

In all three randomized, controlled Asian studies [Takeda _et al._ 2012; Yokoyama _et al._ 2013; Takeda _et al._ 2014], changes from baseline in Qmax were not significantly different for tadalafil 5 mg compared with placebo (Table 1).

The findings of the initial 12-week, double-blind, randomized, placebo-controlled, small pilot study of tadalafil 5 mg once-daily in Korean men [Kim _et al._ 2011] are consistent with those of the other Asian studies, demonstrating numerically greater improvements in the change from baseline to endpoint in total IPSS, IPSS subscores and IPSS QoL index for tadalafil 5 mg compared with placebo (Figure 2; Table 1). As in the other Asian studies, the change from baseline in Qmax was small and not significantly different for tadalafil compared with placebo (Table 1). Integrated analysis of data from Korean men in the pilot study [Kim _et al._ 2011] and the two randomized, controlled trials [Yokoyama _et al._ 2013; Takeda _et al._ 2014] also demonstrated significantly greater improvements in the change from baseline to endpoint in total IPSS, IPSS subscores and IPSS QoL index for tadalafil 5 mg compared with placebo [Lee _et al._ 2014].

The open-label extension of the study of tadalafil 5 mg once-daily carried out in Japanese men (_n_ = 394) [Takeda _et al._ 2012] demonstrated that improvements in total IPSS, IPSS subscores and IPSS QoL index at the end of the 12-week, double-blind, placebo-controlled phase were maintained with long-term treatment (for up to 42 weeks). Although the change in Qmax observed at the end of the double-blind phase was not significantly different for tadalafil 5 mg compared with placebo, Qmax persistently improved with long-term treatment.

To obtain further information on the efficacy of tadalafil in Asian men with BPH-LUTS (specifically, factors that may be considered when prescribing medication for BPH-LUTS in the clinical setting), subgroup analyses by age (<65 years or ⩾65 years), severity of BPH-LUTS at baseline (mild-to-moderate or severe), previous α-blocker therapy within 12 months (yes or no) and prostate volume (<median or ⩾median) were carried out. The three Asian studies [Takeda _et al._ 2012, 2014; Yokoyama _et al._ 2013] and the integrated analyses of data from these studies demonstrated numerically greater improvements in the change from baseline to endpoint in total IPSS for tadalafil 5 mg compared with placebo regardless of age, BPH-LUTS severity, previous α-blocker therapy or prostate volume grouping [Nishizawa _et al_. 2015].

The integrated analyses also demonstrated a number of within subgroup differences regarding total IPSS [Nishizawa _et al_. 2015]. Specifically, the magnitude of improvement was significantly greater for participants aged <65 years compared with participants aged ⩾65 years, whereas symptom severity at the end of treatment was similar in both age categories. Participants who had severe BPH-LUTS at baseline demonstrated numerically greater improvement compared with participants who had mild-to-moderate BPH-LUTS at baseline. Participants who had not received previous α-blocker therapy within 12 months demonstrated numerically greater improvement compared with participants who had received previous α-blocker therapy. Finally, the magnitude of improvement in total IPSS was similar among participants, regardless of prostate volume.

#### Non-Asian studies

The efficacy findings of the randomized, controlled non-Asian studies are generally consistent with those of the randomized, controlled Asian studies (Figure 2a; Table 1). Integrated analysis of data from these non-Asian studies demonstrated significantly greater (_p_ < 0.001) improvement in the change from baseline in total IPSS for tadalafil compared with placebo (placebo = -2.7, tadalafil = -5.0) [Porst _et al._ 2013]. Likewise, there was significantly greater (_p_ < 0.001) improvement in the change from baseline in IPSS storage and voiding subscores and IPSS QoL index for tadalafil compared with placebo [Porst _et al._ 2013]. Interestingly, the integrated analysis also demonstrated a small, but significant (_p_ = 0.003), improvement in the change from baseline in median Qmax for tadalafil compared with placebo [Roehrborn _et al._ 2014]. This significant improvement (_versus_ lack of significance in most individual studies and the integrated analyses of Asian data) likely reflects greater statistical power (_n_ = 752 in the non-Asian studies _versus n_ = 601 in the Asian studies) to detect a small difference and is consistent with tadalafil exerting some effect on SMC relaxation in the prostate or bladder neck. The clinical relevance of such an effect on improvement in BPH-LUTS is unclear [Roehrborn _et al._ 2014].

Subgroup analysis of pooled data from the four non-Asian studies demonstrated significantly greater (_p_ < 0.05) improvement in the change from baseline in total IPSS for tadalafil compared with placebo regardless of baseline age (<65 years _versus_ ⩾65 years), severity of BPH-LUTS, previous α-blocker use within 12 months, or prostate-specific antigen-predicted prostate volume [Porst _et al._ 2013].

Integrated analysis [Oelke _et al._ 2014] of data from the four non-Asian studies demonstrated a small but significant (_p_ = 0.002) improvement in the change from baseline to endpoint in the severity of nocturia (IPSS question 7) for tadalafil 5 mg compared with placebo. However, the treatment difference (–0.2) was not considered to be clinically meaningful.

Integrated analyses [Brock _et al._ 2013, 2014] of data from non-Asian studies have also demonstrated that ED does not affect the LUTS treatment response to tadalafil in men with BPH-LUTS. The impact of ED on the efficacy and safety of tadalafil 5 mg was investigated in an integrated analysis [Brock _et al._ 2013] of data, which included men with BPH-LUTS who had ED and men with BPH-LUTS who did not have ED, from three of the non-Asian studies [Roehrborn _et al._ 2008; Porst _et al._ 2011; Oelke _et al._ 2012]. Significantly greater (_p_ < 0.05) improvements in the change from baseline in total IPSS, IPSS subscores and IPSS QoL index for tadalafil compared with placebo were found, regardless of ED status (treatment-by-ED-status interaction: all _p_ ⩾ 0.687).

More recently, an integrated analysis [Brock _et al._ 2014] of data from all four non-Asian studies [Roehrborn _et al._ 2008; Porst _et al._ 2011; Egerdie _et al._ 2012; Oelke _et al._ 2012] assessed whether the effects of treatment with tadalafil 5 mg for BPH-LUTS were independent of improvements in ED. A weak correlation (_r_ 2 = 0.08) between the change from baseline in total IPSS and the change from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score was detected. Further, unidirectional path analysis revealed that 70% of the improvement in total IPSS was due to a direct effect of tadalafil, whereas 30% of the improvement in total IPSS was due to an indirect effect of tadalafil _via_ improvement in IIEF-EF (_p_ < 0.001). Bidirectional path analysis revealed that 92.5% of the improvement in total IPSS was due to a direct effect of tadalafil, whereas 7.5% of the improvement in total IPSS was due to an indirect effect of tadalafil _via_ improvement in IIEF-EF (_p_ < 0.001). These findings indicate that tadalafil exerts independent effects on BPH-LUTS and ED.

#### Comparison of efficacy with tamsulosin

There are very limited publically available data from 12-week, double-blind, randomized, placebo-controlled studies of tamsulosin in Asian men with BPH-LUTS (Table 2). The available data, mostly from clinical tadalafil studies [Kim _et al._ 2011; Yokoyama _et al._ 2013], demonstrate placebo-adjusted improvement in the change from baseline in total IPSS after treatment with tamsulosin 0.2 mg once-daily ranging from −1.2 to −2.5. In comparison, the placebo-adjusted improvement with tadalafil 5 mg once-daily ranged from −1.1 to −1.7 in the Asian studies [Kim _et al._ 2011; Takeda _et al._ 2012; Yokoyama _et al._ 2013; Takeda _et al._ 2014] (and from −1.9 to −2.6 in the non-Asian studies [Roehrborn _et al._ 2008; Porst _et al._ 2011; Egerdie _et al._ 2012; Oelke _et al._ 2012]). Placebo-adjusted improvements in IPSS subscores and IPSS QoL index were also generally similar for tamsulosin 0.2 mg and tadalafil 5 mg in the Asian studies. Changes from baseline in Qmax were generally small in the placebo-controlled studies of tamsulosin and the Asian studies of tadalafil. Although Qmax has historically been a commonly reported measure in studies examining medical therapies for BPH-LUTS, it is worth noting that both the American Urological Association guideline for the management of BPH and the JUA BPH guidelines indicate that increases in Qmax are poorly correlated with symptomatic improvement [American Urological Association Practice Guidelines Committee, 2010; Homma _et al._ 2011]

##### Table 2.

Mean changes from baseline to end point in total IPSS, IPSS subscores, IPSS quality of life index, and maximum flow rate in 12-week, double-blind, randomized, placebo-controlled clinical studies of tamsulosin in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Study | Treatment | _n_ | Mean change from baseline

* * *  
  
---|---|---|---  
|  |  | Total IPSS | IPSS storage subscore | IPSS voiding subscore | IPSS QoL index | Qmax, ml/s  
Asian studies$ |  |  |  |  |  |  |   
Yokoyama _et al._ [2013] | Placebo | 154 | −3.0 | −1.1 | −1.9 | −0.5 | 2.1  
| Tadalafil 5 mg | 155 | −4.7* | −1.7* | −3.0* | −0.8* | 1.3  
| Tamsulosin 0.2 mg | 152 | −5.5 | −1.7 | −3.8 | −1.1 | 2.1  
Kawabe _et al_. [2006] | Placebo | 89 | −5.3 | −1.5 | −3.8 | −1.1 | 0.3  
| Tamsulosin 0.2 mg | 192 | −6.8 | −2.1 | −4.8 | −1.4 | 2.6  
Kim _et al._ [2011] | Placebo | 51 | −4.2 | −1.5 | −2.7 | −0.9 | 2.3  
| Tadalafil 5 mg | 51 | −5.8 | −2.1 | −3.7 | −1.2 | 2.5  
| Tamsulosin 0.2 mg | 49 | −5.4 | −1.8 | −3.6 | −1.0 | 2.1  
Non-Asian study |  |  |  |  |  |  |   
Oelke _et al._ [2012] | Placebo | 172 | −4.2 | −1.6 | −2.6 | −1.0 | 1.2  
| Tadalafil 5 mg | 171 | −6.3* | −2.2 | −4.1* | −1.3* | 2.4*  
| Tamsulosin 0.4 mg | 168 | −5.7* | −2.2 | −3.5* | −1.1 | 2.2*  
  
[Open in a new tab](table/table2-1756287215589238/)

*

_p_ < 0.05 _versus_ placebo.

$

Tamsulosin _versus_ placebo statistical comparisons were not made in the studies reported by Kawabe _et al_. [2006] and Yokoyama _et al_. [2013].

IPSS, International Prostate Symptom Score; _n_ , number of randomized participants; Qmax, maximum urinary flow rate; QoL, quality of life.

The available data from Asian studies of men with BPH-LUTS suggest that tadalafil 5 mg once-daily for 12 weeks results in improvements in total IPSS, IPSS subscores and IPSS QoL index that are generally similar to those observed with tamsulosin 0.2 mg once-daily. In comparison, a 12-week, double-blind, randomized, placebo-controlled, non-Asian study of tadalafil 5 mg or tamsulosin 0.4 mg once-daily in men with BPH-LUTS [Oelke _et al._ 2012] demonstrated a placebo-adjusted improvement in the change from baseline in total IPSS of −2.1 for tadalafil 5 mg and −1.5 for tamsulosin 0.4 mg (Table 2).

#### Summary

The 12-week Asian studies demonstrated consistently greater improvements in the change from baseline in total IPSS, IPSS subscores and IPSS QoL index for tadalafil 5 mg compared with placebo in men with BPH-LUTS. The improvements at 12 weeks were maintained for 42 weeks, demonstrating the long-term efficacy of tadalafil 5 mg. Furthermore, the greater improvements were apparent regardless of age, severity of BPH-LUTS, previous α-blocker therapy, or prostate volume subgroupings. These findings are consistent with the efficacy findings from the non-Asian studies of tadalafil 5 mg once-daily in men BPH-LUTS and demonstrate that tadalafil 5 mg once-daily is an efficacious treatment for Asian men with BPH-LUTS.

### Safety

To date, three randomized, controlled studies [Takeda _et al._ 2012, 2014; Yokoyama _et al._ 2013], a randomized, controlled pilot study [Kim _et al._ 2011, and an open-label extension study [Takeda _et al._ 2012] have investigated the safety and tolerability of tadalafil 5 mg once-daily as a treatment for BPH-LUTS in men from Asian countries, whereas four randomized, controlled studies have investigated the safety and tolerability of tadalafil 5 mg in men from non-Asian countries [Roehrborn _et al._ 2008; Porst _et al._ 2011; Egerdie _et al._ 2012; Oelke _et al._ 2012]. A randomized, controlled study has also investigated the urodynamic safety of tadalafil 20 mg once-daily in men from non-Asian countries [Dmochowski _et al._ 2010].

#### Asian studies

Tadalafil 5 mg was well tolerated in the randomized, controlled Asian studies [Takeda _et al._ 2012, 2014; Yokoyama _et al._ 2013] and had a safety profile consistent with the known safety profile of tadalafil as per the current package insert for tadalafil (Cialis) 5 mg to 20 mg as needed for ED [Eli Lilly Japan, 2012]. Integrated analysis of safety data from these studies demonstrated that the most common treatment-emergent adverse events (TEAEs) were nasopharyngitis, dyspepsia and headache (Table 3). Few participants experienced serious adverse events (placebo = 0.5%, tadalafil = 0.7%; none were considered to be treatment-related) or TEAEs leading to discontinuation (placebo = 2.7%, tadalafil = 1.8%).

##### Table 3.

Treatment-emergent adverse events reported by ⩾2% of participants in 12-week, double-blind, randomized, placebo-controlled clinical studies of tadalafil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Common TEAEs | Asian studies*

* * *

| Non-Asian studies$

* * *  
  
---|---|---  
| Placebo (_n_ = 598) | Tadalafil 5 mg(_n_ = 601) | Placebo (_n_ = 748) | Tadalafil 5 mg (_n_ = 752)  
Dyspepsia | 0.3% | 3.0% | 0.1% | 2.4%  
Headache | 1.7% | 2.5% | 2.0% | 3.9%  
Nasopharyngitis | 5.4% | 4.8% | 2.3% | 2.3%  
  
[Open in a new tab](table/table3-1756287215589238/)

*

Safety dataset pooled from all participants in the Asian studies [Takeda _et al._ 2012, 2014; Yokoyama _et al._ 2013].

$

Safety dataset pooled from all participants in the non-Asian studies [Roehrborn _et al._ 2008; Porst _et al._ 2011; Egerdie _et al._ 2012; Oelke _et al._ 2012].

_n_ , number of randomized participants; TEAEs, treatment-emergent adverse events.

The type and frequency of individual TEAEs in the pilot study [Kim _et al._ 2011] were similar to those reported in the randomized, controlled Asian studies. No new or unexpected safety findings were observed with longer term treatment [Takeda _et al._ 2012].

Subgroup analysis of data from the three randomized, controlled Asian studies demonstrated that there were no meaningful differences in safety findings by age, ethnicity, pre-existing disease, renal function, or previous α-blocker therapy [unpublished data].

#### Non-Asian studies

The safety and tolerability findings of the non-Asian studies are consistent with those of the Asian studies. Integrated analysis of data from the non-Asian studies of tadalafil 5 mg demonstrated that the most common TEAEs were headache, back pain (placebo = 1.2%, tadalafil = 2.4%), dyspepsia and nasopharyngitis (Table 3). As in the Asian studies, few participants experienced serious adverse events (placebo = 0.7%, tadalafil = 0.8%) or TEAEs leading to discontinuation (placebo = 1.5%, tadalafil = 3.1%).

The findings from the double-blind, placebo-controlled, 12-week, invasive/noninvasive urodynamic study [Dmochowski _et al._ 2010] of tadalafil 20 mg in men with BPH-LUTS (with and without bladder outlet obstruction) indicate that tadalafil has no negative effects on bladder function. In this study, there were no statistically significant or clinically adverse differences between tadalafil and placebo in change in detrusor pressure at Qmax, mean urine flow, voided volume, maximum detrusor pressure during voiding, postvoid residual volume, total bladder capacity, bladder voiding efficiency, bladder contractility index, bladder outlet obstruction index, presence of involuntary detrusor contractions during bladder filling, or bladder volume at first involuntary detrusor contraction. As participants with detrusor overactivity were not excluded or proactively enrolled and the frequency or amplitude of detrusor contractions were not assessed, no conclusions can be made from the results of this study regarding the effects of tadalafil on detrusor overactivity.

#### Summary

Tadalafil was well tolerated and no new safety concerns were identified in any of the Asian studies. The safety findings from the non-Asian studies of tadalafil 5 mg once-daily in men with BPH-LUTS are consistent with the corresponding findings from the Asian studies.

## Tadalafil combination therapy

### Tadalafil/α-blocker combination therapy

No large, double-blind, placebo-controlled study has assessed the efficacy of tadalafil/α-blocker combination therapy. However, several small clinical studies have reported that tadalafil/α-blocker combination therapy may provide greater improvement in the change from baseline in total IPSS than α-blocker therapy alone [Bechara _et al._ 2008; Liguori _et al._ 2009] or tadalafil therapy alone [Liguori _et al._ 2009; Singh _et al._ 2014] in men with BPH-LUTS. However, these studies either included a small number of participants, involved tadalafil doses >5 mg once-daily, and/or were not placebo controlled.

The safety of tadalafil 5 mg in combination with α-blockers (alfuzosin, silodosin, tamsulosin, doxazosin or terazosin) was investigated in a US double-blind, randomized, placebo-controlled trial of men with BPH-LUTS (tadalafil/α-blocker, _n_ = 158; placebo, _n_ = 160) [Goldfischer _et al._ 2012]. This study was not designed to assess efficacy. No new safety concerns were identified for tadalafil/α-blocker combination therapy in this study. Furthermore, the proportion of participants reporting treatment-emergent dizziness or with a positive orthostatic test was similar between the tadalafil/α-blocker combination therapy group and the placebo/α-blocker combination therapy group.

Note that combining doxazosin with tadalafil is not recommended (per the package inserts for Cialis and Zalutia) as tadalafil may potentiate the hypotensive effects of this non-uroselective α-blocker [Kloner _et al_. 2004; Guillaume _et al_. 2007; Eli Lilly Japan, 2014].

### Tadalafil/5ARI combination therapy

Several clinical studies have examined the efficacy and safety of tadalafil/5ARI combination therapy, with simultaneous initiation, in men with an enlarged prostate and BPH-LUTS. In a multinational, randomized, double-blind, 26-week study of finasteride 5 mg/tadalafil 5 mg (_n_ = 346) compared with finasteride 5 mg/placebo (_n_ = 350) [Roehrborn _et al_. 2015; Casabe _et al._ 2014; Glina _et al._ 2014], there was significantly greater (_p_ < 0.05) improvement in the change from baseline in total IPSS for finasteride/tadalafil compared with finasteride/placebo at weeks 4, 12 and 26 [Casabe _et al._ 2014]. There were also significant treatment differences in secondary outcomes assessed, including the change from baseline in the IPSS voiding subscore for finasteride/tadalafil compared with finasteride/placebo at weeks 4, 12, and 26, the IPSS storage subscore at weeks 4 and 12 and IPSS QoL index at week 4. Furthermore, participants who received finasteride/tadalafil were significantly more satisfied with their treatment (Treatment Satisfaction Scale-BPH) at week 26 than participants who received finasteride/placebo [Roehrborn _et al._ 2015]. In a small, 12-week, Korean, randomized study, a similar magnitude of improvement in the change from baseline in total IPSS at week 12 was found for tadalafil 5 mg/dutasteride 0.5 mg (−2.3, _n_ = 86) compared with tamsulosin 0.2 mg/dutasteride 0.5 mg (−2.5, _n_ = 82) [Park and Park, 2013].

No new safety concerns were identified for tadalafil/5ARI combination therapy in either of these studies [Park and Park, 2013; Casabe _et al._ 2014]. In the 26-week study, a lower proportion of participants who received finasteride/tadalafil discontinued compared with participants who received finasteride/placebo [Casabe _et al._ 2014]. Few participants in either group reported adverse events related to sexual dysfunction [Glina _et al._ 2014].

The findings from these studies suggest that tadalafil/5ARI combination therapy may result in earlier and greater improvement in BPH-LUTS compared with 5ARI therapy alone [Casabe _et al._ 2014] and that tadalafil/dutasteride combination therapy may result in similar improvements in BPH-LUTS compared with tamsulosin/dutasteride combination therapy [Park and Park, 2013].

### Summary

The available data from large, well-controlled studies suggest that tadalafil/5ARI combination therapy provides added benefit in the treatment of BPH-LUTS compared with 5ARI monotherapy and that both tadalafil/α-blocker and tadalafil/5ARI combination therapy have favorable safety profiles.

## Conclusion

Studies have shown that the inhibition of PDE5 isoenzymes relaxes smooth muscle in the prostate and bladder neck (_via_ cGMP), increases blood perfusion to the prostate and bladder, and decreases bladder afferent nerve activity. These underlying effects of tadalafil are in keeping with the findings from clinical studies, which have demonstrated that tadalafil relieves BPH-LUTS. Specifically, clinical studies carried out in Asian and non-Asian countries have demonstrated that tadalafil 5 mg once-daily is an efficacious treatment for men with BPH-LUTS and has a safety profile consistent with the known safety profile of tadalafil for ED. These findings support tadalafil monotherapy for men, including Asian men, with BPH-LUTS. Clinical studies also suggest that tadalafil/5ARI combination therapy may be more efficacious than 5ARI monotherapy, and that tadalafil/5ARI and tadalafil/uroselective α-blocker combination therapy have favorable safety profiles.

## Acknowledgments

We thank Yukiko Inoue for editorial support.

## Footnotes

**Funding:** Medical writing assistance was provided by Luke Carey, PhD, and Serina Stretton, PhD, CMPP, of ProScribe – part of the Envision Pharma Group, and was funded by Eli Lilly Japan K.K. (Eli Lilly and Company is the manufacturer of tadalafil). ProScribe’s services complied with international guidelines for Good Publication Practice (GPP2).

**Conflict of interest statement:** T.Y. and M.M. are employees of Eli Lilly Japan K.K. L.V. is an employee of Eli Lilly and Company. O.Y., Y.I. and M.T. have been advisory board members for Eli Lilly Japan K.K. M.M. and L.V. are stockholders of Eli Lilly and Company.

## Contributor Information

Osamu Yokoyama, Department of Urology, Faculty of Medical Science, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.

Yasuhiko Igawa, Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Masayuki Takeda, Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.

Takafumi Yamaguchi, Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Hyogo, Japan.

Masahiro Murakami, Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Hyogo, Japan.

Lars Viktrup, Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana, USA.

## References

  1. Abdelwahab O., El-Barky E., Khalil M., Kamar A. (2012) Evaluation of the resistive index of prostatic blood flow in benign prostatic hyperplasia. Int Braz J Urol 38: 250–255; discussion 255–257. [[DOI](https://doi.org/10.1590/s1677-55382012000200014)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22555031/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20Braz%20J%20Urol&title=Evaluation%20of%20the%20resistive%20index%20of%20prostatic%20blood%20flow%20in%20benign%20prostatic%20hyperplasia&author=O.%20Abdelwahab&author=E.%20El-Barky&author=M.%20Khalil&author=A.%20Kamar&volume=38&publication_year=2012&pages=250-255&pmid=22555031&doi=10.1590/s1677-55382012000200014&)]
  2. Abrams P., Cardozo L., Fall M., Griffiths D., Rosier P., Ulmsten U., et al. (2003) The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology 61: 37–49. [[DOI](https://doi.org/10.1016/s0090-4295\(02\)02243-4)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/12559262/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Urology&title=The%20standardisation%20of%20terminology%20in%20lower%20urinary%20tract%20function:%20report%20from%20the%20standardisation%20sub-committee%20of%20the%20International%20Continence%20Society&author=P.%20Abrams&author=L.%20Cardozo&author=M.%20Fall&author=D.%20Griffiths&author=P.%20Rosier&volume=61&publication_year=2003&pages=37-49&pmid=12559262&doi=10.1016/s0090-4295\(02\)02243-4&)]
  3. Adolfsson P., Ahlstrand C., Varenhorst E., Svensson S. (2002) Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: sildenafil and papaverin generate inhibition. Prostate 51: 50–58. [[DOI](https://doi.org/10.1002/pros.10077)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11920958/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Prostate&title=Lysophosphatidic%20acid%20stimulates%20proliferation%20of%20cultured%20smooth%20muscle%20cells%20from%20human%20BPH%20tissue:%20sildenafil%20and%20papaverin%20generate%20inhibition&author=P.%20Adolfsson&author=C.%20Ahlstrand&author=E.%20Varenhorst&author=S.%20Svensson&volume=51&publication_year=2002&pages=50-58&pmid=11920958&doi=10.1002/pros.10077&)]
  4. American Urological Association Practice Guidelines Committee (2010) American Urological Association Guideline: Management of benign prostatic hyperplasia (BPH). Linthicum, MD: American Urological Association; Available at: <https://www.auanet.org/education/guidelines/benign-prostatic-hyperplasia.cfm> (accessed 23 June 2014). [[Google Scholar](https://scholar.google.com/scholar_lookup?title=American%20Urological%20Association%20Guideline:%20Management%20of%20benign%20prostatic%20hyperplasia%20\(BPH\)&publication_year=2010&)]
  5. Andersson K., De Groat W., McVary K., Lue T., Maggi M., Roehrborn C., et al. (2011) Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action. Neurourol Urodyn 30: 292–301. [[DOI](https://doi.org/10.1002/nau.20999)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21284024/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Neurourol%20Urodyn&title=Tadalafil%20for%20the%20treatment%20of%20lower%20urinary%20tract%20symptoms%20secondary%20to%20benign%20prostatic%20hyperplasia:%20pathophysiology%20and%20mechanism\(s\)%20of%20action&author=K.%20Andersson&author=W.%20De%20Groat&author=K.%20McVary&author=T.%20Lue&author=M.%20Maggi&volume=30&publication_year=2011&pages=292-301&pmid=21284024&doi=10.1002/nau.20999&)]
  6. Angulo J., Cuevas P., Fernandez A., La Fuente J., Allona A., Moncada I., et al. (2012) Tadalafil enhances the inhibitory effects of tamsulosin on neurogenic contractions of human prostate and bladder neck. J Sex Med 9: 2293–2306. [[DOI](https://doi.org/10.1111/j.1743-6109.2012.02821.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22759598/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Tadalafil%20enhances%20the%20inhibitory%20effects%20of%20tamsulosin%20on%20neurogenic%20contractions%20of%20human%20prostate%20and%20bladder%20neck&author=J.%20Angulo&author=P.%20Cuevas&author=A.%20Fernandez&author=J.%20La%20Fuente&author=A.%20Allona&volume=9&publication_year=2012&pages=2293-2306&pmid=22759598&doi=10.1111/j.1743-6109.2012.02821.x&)]
  7. Barry M., Fowler F., Jr., O’Leary M., Bruskewitz R., Holtgrewe H., Mebust W., et al. (1992) The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol 148: 1549–1557. [[DOI](https://doi.org/10.1016/s0022-5347\(17\)36966-5)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/1279218/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=The%20American%20Urological%20Association%20symptom%20index%20for%20benign%20prostatic%20hyperplasia.%20The%20Measurement%20Committee%20of%20the%20American%20Urological%20Association&author=M.%20Barry&author=F.%20Fowler&author=M.%20O%E2%80%99Leary&author=R.%20Bruskewitz&author=H.%20Holtgrewe&volume=148&publication_year=1992&pages=1549-1557&pmid=1279218&doi=10.1016/s0022-5347\(17\)36966-5&)]
  8. Bechara A., Romano S., Casabe A., Haime S., Dedola P., Hernandez C., et al. (2008) Comparative efficacy assessment of tamsulosin _versus_. tamsulosin plus tadalafil in the treatment of LUTS/BPH. Pilot study. J Sex Med 5: 2170–2178. [[DOI](https://doi.org/10.1111/j.1743-6109.2008.00940.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18638006/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Comparative%20efficacy%20assessment%20of%20tamsulosin%20versus.%20tamsulosin%20plus%20tadalafil%20in%20the%20treatment%20of%20LUTS/BPH.%20Pilot%20study&author=A.%20Bechara&author=S.%20Romano&author=A.%20Casabe&author=S.%20Haime&author=P.%20Dedola&volume=5&publication_year=2008&pages=2170-2178&pmid=18638006&doi=10.1111/j.1743-6109.2008.00940.x&)]
  9. Behr-Roussel D., Oger S., Caisey S., Sandner P., Bernabe J., Alexandre L., et al. (2011) Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats. Eur Urol 59: 272–279. [[DOI](https://doi.org/10.1016/j.eururo.2010.10.037)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21036463/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Vardenafil%20decreases%20bladder%20afferent%20nerve%20activity%20in%20unanesthetized,%20decerebrate,%20spinal%20cord-injured%20rats&author=D.%20Behr-Roussel&author=S.%20Oger&author=S.%20Caisey&author=P.%20Sandner&author=J.%20Bernabe&volume=59&publication_year=2011&pages=272-279&pmid=21036463&doi=10.1016/j.eururo.2010.10.037&)]
  10. Berger A., Deibl M., Leonhartsberger N., Bektic J., Horninger W., Fritsche G., et al. (2005) Vascular damage as a risk factor for benign prostatic hyperplasia and erectile dysfunction. BJU Int 96: 1073–1078. [[DOI](https://doi.org/10.1111/j.1464-410X.2005.05777.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16225531/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=Vascular%20damage%20as%20a%20risk%20factor%20for%20benign%20prostatic%20hyperplasia%20and%20erectile%20dysfunction&author=A.%20Berger&author=M.%20Deibl&author=N.%20Leonhartsberger&author=J.%20Bektic&author=W.%20Horninger&volume=96&publication_year=2005&pages=1073-1078&pmid=16225531&doi=10.1111/j.1464-410X.2005.05777.x&)]
  11. Bertolotto M., Trincia E., Zappetti R., Bernich R., Savoca G., Cova M. (2009) Effect of tadalafil on prostate haemodynamics: preliminary evaluation with contrast-enhanced US. Radiol Med 114: 1106–1114. [[DOI](https://doi.org/10.1007/s11547-009-0449-8)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19697101/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Radiol%20Med&title=Effect%20of%20tadalafil%20on%20prostate%20haemodynamics:%20preliminary%20evaluation%20with%20contrast-enhanced%20US&author=M.%20Bertolotto&author=E.%20Trincia&author=R.%20Zappetti&author=R.%20Bernich&author=G.%20Savoca&volume=114&publication_year=2009&pages=1106-1114&pmid=19697101&doi=10.1007/s11547-009-0449-8&)]
  12. Bittencourt J., Tano T., Gajar S., Resende A., De Lemos Neto M., Damiao R., et al. (2009) Relaxant effects of sildenafil on the human isolated bladder neck. Urology 73: 427–430. [[DOI](https://doi.org/10.1016/j.urology.2008.06.060)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18774591/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Urology&title=Relaxant%20effects%20of%20sildenafil%20on%20the%20human%20isolated%20bladder%20neck&author=J.%20Bittencourt&author=T.%20Tano&author=S.%20Gajar&author=A.%20Resende&author=M.%20De%20Lemos%20Neto&volume=73&publication_year=2009&pages=427-430&pmid=18774591&doi=10.1016/j.urology.2008.06.060&)]
  13. Brock G., Broderick G., Roehrborn C., Xu L., Wong D., Viktrup L. (2013) Tadalafil once daily in the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in men without erectile dysfunction. BJU Int 112: 990–997. [[DOI](https://doi.org/10.1111/bju.12251)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/23937669/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=Tadalafil%20once%20daily%20in%20the%20treatment%20of%20lower%20urinary%20tract%20symptoms%20\(LUTS\)%20suggestive%20of%20benign%20prostatic%20hyperplasia%20\(BPH\)%20in%20men%20without%20erectile%20dysfunction&author=G.%20Brock&author=G.%20Broderick&author=C.%20Roehrborn&author=L.%20Xu&author=D.%20Wong&volume=112&publication_year=2013&pages=990-997&pmid=23937669&doi=10.1111/bju.12251&)]
  14. Brock G., McVary K., Roehrborn C., Watts S., Ni X., Viktrup L., et al. (2014) Direct effects of tadalafil on lower urinary tract symptoms _versus_ indirect effects mediated through erectile dysfunction symptom improvement: integrated data analyses from 4 placebo controlled clinical studies. J Urol 191: 405–411. [[DOI](https://doi.org/10.1016/j.juro.2013.09.057)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24096120/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Direct%20effects%20of%20tadalafil%20on%20lower%20urinary%20tract%20symptoms%20versus%20indirect%20effects%20mediated%20through%20erectile%20dysfunction%20symptom%20improvement:%20integrated%20data%20analyses%20from%204%20placebo%20controlled%20clinical%20studies&author=G.%20Brock&author=K.%20McVary&author=C.%20Roehrborn&author=S.%20Watts&author=X.%20Ni&volume=191&publication_year=2014&pages=405-411&pmid=24096120&doi=10.1016/j.juro.2013.09.057&)]
  15. Casabe A., Roehrborn C., Da Pozzo L., Zepeda S., Henderson R., Sorsaburu S., et al. (2014) Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia. J Urol 191: 727–733. [[DOI](https://doi.org/10.1016/j.juro.2013.09.059)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24096118/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Efficacy%20and%20safety%20of%20the%20coadministration%20of%20tadalafil%20once%20daily%20with%20finasteride%20for%206%20months%20in%20men%20with%20lower%20urinary%20tract%20symptoms%20and%20prostatic%20enlargement%20secondary%20to%20benign%20prostatic%20hyperplasia&author=A.%20Casabe&author=C.%20Roehrborn&author=L.%20Da%20Pozzo&author=S.%20Zepeda&author=R.%20Henderson&volume=191&publication_year=2014&pages=727-733&pmid=24096118&doi=10.1016/j.juro.2013.09.059&)]
  16. Cortijo J., Naline E., Ortiz J., Berto L., Girard V., Malbezin M., et al. (1998) Effects of fenspiride on human bronchial cyclic nucleotide phosphodiesterase isoenzymes: functional and biochemical study. Eur J Pharmacol 341: 79–86. [[DOI](https://doi.org/10.1016/s0014-2999\(97\)01439-8)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9489859/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20J%20Pharmacol&title=Effects%20of%20fenspiride%20on%20human%20bronchial%20cyclic%20nucleotide%20phosphodiesterase%20isoenzymes:%20functional%20and%20biochemical%20study&author=J.%20Cortijo&author=E.%20Naline&author=J.%20Ortiz&author=L.%20Berto&author=V.%20Girard&volume=341&publication_year=1998&pages=79-86&pmid=9489859&doi=10.1016/s0014-2999\(97\)01439-8&)]
  17. Coyne K., Sexton C., Thompson C., Milsom I., Irwin D., Kopp Z., et al. (2009) The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. BJU Int 104: 352–360. [[DOI](https://doi.org/10.1111/j.1464-410X.2009.08427.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19281467/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=The%20prevalence%20of%20lower%20urinary%20tract%20symptoms%20\(LUTS\)%20in%20the%20USA,%20the%20UK%20and%20Sweden:%20results%20from%20the%20Epidemiology%20of%20LUTS%20\(EpiLUTS\)%20study&author=K.%20Coyne&author=C.%20Sexton&author=C.%20Thompson&author=I.%20Milsom&author=D.%20Irwin&volume=104&publication_year=2009&pages=352-360&pmid=19281467&doi=10.1111/j.1464-410X.2009.08427.x&)]
  18. De Nunzio C., Aronson W., Freedland S., Giovannucci E., Parsons J. (2012) The correlation between metabolic syndrome and prostatic diseases. Eur Urol 61: 560–570. [[DOI](https://doi.org/10.1016/j.eururo.2011.11.013)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22119157/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=The%20correlation%20between%20metabolic%20syndrome%20and%20prostatic%20diseases&author=C.%20De%20Nunzio&author=W.%20Aronson&author=S.%20Freedland&author=E.%20Giovannucci&author=J.%20Parsons&volume=61&publication_year=2012&pages=560-570&pmid=22119157&doi=10.1016/j.eururo.2011.11.013&)]
  19. Dmochowski R., Roehrborn C., Klise S., Xu L., Kaminetsky J., Kraus S. (2010) Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial. J Urol 183: 1092–1097. [[DOI](https://doi.org/10.1016/j.juro.2009.11.014)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/20092847/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Urodynamic%20effects%20of%20once%20daily%20tadalafil%20in%20men%20with%20lower%20urinary%20tract%20symptoms%20secondary%20to%20clinical%20benign%20prostatic%20hyperplasia:%20a%20randomized,%20placebo%20controlled%2012-week%20clinical%20trial&author=R.%20Dmochowski&author=C.%20Roehrborn&author=S.%20Klise&author=L.%20Xu&author=J.%20Kaminetsky&volume=183&publication_year=2010&pages=1092-1097&pmid=20092847&doi=10.1016/j.juro.2009.11.014&)]
  20. Donatucci C., Brock G., Goldfischer E., Pommerville P., Elion-Mboussa A., Kissel J., et al. (2011) Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1-year, open-label extension study. BJU Int 107: 1110–1116. [[DOI](https://doi.org/10.1111/j.1464-410X.2010.09687.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21244606/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=Tadalafil%20administered%20once%20daily%20for%20lower%20urinary%20tract%20symptoms%20secondary%20to%20benign%20prostatic%20hyperplasia:%20a%201-year,%20open-label%20extension%20study&author=C.%20Donatucci&author=G.%20Brock&author=E.%20Goldfischer&author=P.%20Pommerville&author=A.%20Elion-Mboussa&volume=107&publication_year=2011&pages=1110-1116&pmid=21244606&doi=10.1111/j.1464-410X.2010.09687.x&)]
  21. Egerdie R., Auerbach S., Roehrborn C., Costa P., Garza M., Esler A., et al. (2012) Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: results of a randomized, placebo-controlled, double-blind study. J Sex Med 9: 271–281. [[DOI](https://doi.org/10.1111/j.1743-6109.2011.02504.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21981682/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Tadalafil%202.5%20or%205%20mg%20administered%20once%20daily%20for%2012%20weeks%20in%20men%20with%20both%20erectile%20dysfunction%20and%20signs%20and%20symptoms%20of%20benign%20prostatic%20hyperplasia:%20results%20of%20a%20randomized,%20placebo-controlled,%20double-blind%20study&author=R.%20Egerdie&author=S.%20Auerbach&author=C.%20Roehrborn&author=P.%20Costa&author=M.%20Garza&volume=9&publication_year=2012&pages=271-281&pmid=21981682&doi=10.1111/j.1743-6109.2011.02504.x&)]
  22. Eli Lilly Japan (2012) Cialis. Package insert. Kobe, Japan: Eli Lilly Japan K.K. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Cialis.%20Package%20insert&publication_year=2012&)]
  23. Eli Lilly Japan (2014) Zalutia. Package insert. Kobe, Japan: Eli Lilly Japan K.K. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Zalutia.%20Package%20insert&publication_year=2014&)]
  24. Fibbi B., Morelli A., Vignozzi L., Filippi S., Chavalmane A., De Vita G., et al. (2010) Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 7: 59–69. [[DOI](https://doi.org/10.1111/j.1743-6109.2009.01511.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19796053/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Characterization%20of%20phosphodiesterase%20type%205%20expression%20and%20functional%20activity%20in%20the%20human%20male%20lower%20urinary%20tract&author=B.%20Fibbi&author=A.%20Morelli&author=L.%20Vignozzi&author=S.%20Filippi&author=A.%20Chavalmane&volume=7&publication_year=2010&pages=59-69&pmid=19796053&doi=10.1111/j.1743-6109.2009.01511.x&)]
  25. Filippi S., Morelli A., Sandner P., Fibbi B., Mancina R., Marini M., et al. (2007) Characterization and functional role of androgen-dependent PDE5 activity in the bladder. Endocrinology 148: 1019–1029. [[DOI](https://doi.org/10.1210/en.2006-1079)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17138653/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Endocrinology&title=Characterization%20and%20functional%20role%20of%20androgen-dependent%20PDE5%20activity%20in%20the%20bladder&author=S.%20Filippi&author=A.%20Morelli&author=P.%20Sandner&author=B.%20Fibbi&author=R.%20Mancina&volume=148&publication_year=2007&pages=1019-1029&pmid=17138653&doi=10.1210/en.2006-1079&)]
  26. Francis S., Busch J., Corbin J., Sibley D. (2010) cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev 62: 525–563. [[DOI](https://doi.org/10.1124/pr.110.002907)] [[PMC free article](/articles/PMC2964902/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/20716671/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Pharmacol%20Rev&title=cGMP-dependent%20protein%20kinases%20and%20cGMP%20phosphodiesterases%20in%20nitric%20oxide%20and%20cGMP%20action&author=S.%20Francis&author=J.%20Busch&author=J.%20Corbin&author=D.%20Sibley&volume=62&publication_year=2010&pages=525-563&pmid=20716671&doi=10.1124/pr.110.002907&)]
  27. Fullhase C., Hennenberg M., Giese A., Schmidt M., Strittmatter F., Soler R., et al. (2013) Presence of phosphodiesterase type 5 in the spinal cord and its involvement in bladder outflow obstruction related bladder overactivity. J Urol 190: 1430–1435. [[DOI](https://doi.org/10.1016/j.juro.2013.03.112)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/23545097/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Presence%20of%20phosphodiesterase%20type%205%20in%20the%20spinal%20cord%20and%20its%20involvement%20in%20bladder%20outflow%20obstruction%20related%20bladder%20overactivity&author=C.%20Fullhase&author=M.%20Hennenberg&author=A.%20Giese&author=M.%20Schmidt&author=F.%20Strittmatter&volume=190&publication_year=2013&pages=1430-1435&pmid=23545097&doi=10.1016/j.juro.2013.03.112&)]
  28. Gacci M., Corona G., Vignozzi L., Salvi M., Serni S., De Nunzio C., et al. (2015) Metabolic syndrome and benign prostatic enlargement: a systematic review and meta-analysis. BJU Int 115: 24–31. [[DOI](https://doi.org/10.1111/bju.12728)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24602293/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=Metabolic%20syndrome%20and%20benign%20prostatic%20enlargement:%20a%20systematic%20review%20and%20meta-analysis&author=M.%20Gacci&author=G.%20Corona&author=L.%20Vignozzi&author=M.%20Salvi&author=S.%20Serni&volume=115&publication_year=2015&pages=24-31&pmid=24602293&doi=10.1111/bju.12728&)]
  29. Giuliano F., Uckert S., Maggi M., Birder L., Kissel J., Viktrup L. (2013) The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol 63: 506–516. [[DOI](https://doi.org/10.1016/j.eururo.2012.09.006)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/23018163/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=The%20mechanism%20of%20action%20of%20phosphodiesterase%20type%205%20inhibitors%20in%20the%20treatment%20of%20lower%20urinary%20tract%20symptoms%20related%20to%20benign%20prostatic%20hyperplasia&author=F.%20Giuliano&author=S.%20Uckert&author=M.%20Maggi&author=L.%20Birder&author=J.%20Kissel&volume=63&publication_year=2013&pages=506-516&pmid=23018163&doi=10.1016/j.eururo.2012.09.006&)]
  30. Glina S., Roehrborn C., Esen A., Plekhanov A., Sorsaburu S., Henneges C., et al. (2014) Sexual function in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: results of a 6-month, randomized, double-blind, placebo-controlled study of tadalafil co-administered with finasteride. J Sex Med 12: 129–138. [[DOI](https://doi.org/10.1111/jsm.12714)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/25353053/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Sexual%20function%20in%20men%20with%20lower%20urinary%20tract%20symptoms%20and%20prostatic%20enlargement%20secondary%20to%20benign%20prostatic%20hyperplasia:%20results%20of%20a%206-month,%20randomized,%20double-blind,%20placebo-controlled%20study%20of%20tadalafil%20co-administered%20with%20finasteride&author=S.%20Glina&author=C.%20Roehrborn&author=A.%20Esen&author=A.%20Plekhanov&author=S.%20Sorsaburu&volume=12&publication_year=2014&pages=129-138&pmid=25353053&doi=10.1111/jsm.12714&)]
  31. Goldfischer E., Kowalczyk J., Clark W., Brady E., Shane M., Dgetluck N., et al. (2012) Hemodynamic effects of once-daily tadalafil in men with signs and symptoms of benign prostatic hyperplasia on concomitant alpha1-adrenergic antagonist therapy: results of a multicenter randomized, double-blind, placebo-controlled trial. Urology 79: 875–882. [[DOI](https://doi.org/10.1016/j.urology.2011.11.040)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22341603/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Urology&title=Hemodynamic%20effects%20of%20once-daily%20tadalafil%20in%20men%20with%20signs%20and%20symptoms%20of%20benign%20prostatic%20hyperplasia%20on%20concomitant%20alpha1-adrenergic%20antagonist%20therapy:%20results%20of%20a%20multicenter%20randomized,%20double-blind,%20placebo-controlled%20trial&author=E.%20Goldfischer&author=J.%20Kowalczyk&author=W.%20Clark&author=E.%20Brady&author=M.%20Shane&volume=79&publication_year=2012&pages=875-882&pmid=22341603&doi=10.1016/j.urology.2011.11.040&)]
  32. Guillaume M., Lonsdale F., Darstein C., Jimenez M., Mitchell M. (2007) Hemodynamic interaction between a daily dosed phosphodiesterase 5 inhibitor, tadalafil, and the alpha- adrenergic blockers, doxazosin and tamsulosin, in middle-aged healthy male subjects. J Clin Pharmacol 47: 1303–1310. [[DOI](https://doi.org/10.1177/0091270007306559)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17906163/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Clin%20Pharmacol&title=Hemodynamic%20interaction%20between%20a%20daily%20dosed%20phosphodiesterase%205%20inhibitor,%20tadalafil,%20and%20the%20alpha-%20adrenergic%20blockers,%20doxazosin%20and%20tamsulosin,%20in%20middle-aged%20healthy%20male%20subjects&author=M.%20Guillaume&author=F.%20Lonsdale&author=C.%20Darstein&author=M.%20Jimenez&author=M.%20Mitchell&volume=47&publication_year=2007&pages=1303-1310&pmid=17906163&doi=10.1177/0091270007306559&)]
  33. Haaga J., Exner A., Fei B., Seftel A. (2007) Semiquantitative imaging measurement of baseline and vasomodulated normal prostatic blood flow using sildenafil. Int J Impot Res 19: 110–113. [[DOI](https://doi.org/10.1038/sj.ijir.3901486)] [[PMC free article](/articles/PMC3779690/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16728965/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Impot%20Res&title=Semiquantitative%20imaging%20measurement%20of%20baseline%20and%20vasomodulated%20normal%20prostatic%20blood%20flow%20using%20sildenafil&author=J.%20Haaga&author=A.%20Exner&author=B.%20Fei&author=A.%20Seftel&volume=19&publication_year=2007&pages=110-113&pmid=16728965&doi=10.1038/sj.ijir.3901486&)]
  34. Haslam R., Dickinson N., Jang E. (1999) Cyclic nucleotides and phosphodiesterases in platelets. Thromb Haemost 82: 412–423. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10605732/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Thromb%20Haemost&title=Cyclic%20nucleotides%20and%20phosphodiesterases%20in%20platelets&author=R.%20Haslam&author=N.%20Dickinson&author=E.%20Jang&volume=82&publication_year=1999&pages=412-423&pmid=10605732&)]
  35. Homma Y., Gotoh M., Yokoyama O., Masumori N., Kawauchi A., Yamanishi T., et al. (2011) Outline of JUA clinical guidelines for benign prostatic hyperplasia. Int J Urol 18: 741–756. [[DOI](https://doi.org/10.1111/j.1442-2042.2011.02860.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22050351/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Urol&title=Outline%20of%20JUA%20clinical%20guidelines%20for%20benign%20prostatic%20hyperplasia&author=Y.%20Homma&author=M.%20Gotoh&author=O.%20Yokoyama&author=N.%20Masumori&author=A.%20Kawauchi&volume=18&publication_year=2011&pages=741-756&pmid=22050351&doi=10.1111/j.1442-2042.2011.02860.x&)]
  36. Homma Y., Tsukamoto T., Yasuda K., Ozono S., Yoshida M., Shinji M. (2002) Linguistic validation of Japanese version of International Prostate Symptom Score and BPH impact index. Nippon Hinyokika Gakkai Zasshi 93: 669–680. [[DOI](https://doi.org/10.5980/jpnjurol1989.93.669)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/12385091/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Nippon%20Hinyokika%20Gakkai%20Zasshi&title=Linguistic%20validation%20of%20Japanese%20version%20of%20International%20Prostate%20Symptom%20Score%20and%20BPH%20impact%20index&author=Y.%20Homma&author=T.%20Tsukamoto&author=K.%20Yasuda&author=S.%20Ozono&author=M.%20Yoshida&volume=93&publication_year=2002&pages=669-680&pmid=12385091&doi=10.5980/jpnjurol1989.93.669&)]
  37. Irwin D., Milsom I., Hunskaar S., Reilly K., Kopp Z., Herschorn S., et al. (2006) Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 50: 1306–1314; discussion 1314–1305. [[DOI](https://doi.org/10.1016/j.eururo.2006.09.019)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17049716/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Population-based%20survey%20of%20urinary%20incontinence,%20overactive%20bladder,%20and%20other%20lower%20urinary%20tract%20symptoms%20in%20five%20countries:%20results%20of%20the%20EPIC%20study&author=D.%20Irwin&author=I.%20Milsom&author=S.%20Hunskaar&author=K.%20Reilly&author=Z.%20Kopp&volume=50&publication_year=2006&pages=1306-1314&pmid=17049716&doi=10.1016/j.eururo.2006.09.019&)]
  38. Jacobsen S., Guess H., Panser L., Girman C., Chute C., Oesterling J., et al. (1993) A population-based study of health care-seeking behavior for treatment of urinary symptoms. The Olmsted County Study of Urinary Symptoms and Health Status Among Men. Arch Fam Med 2: 729–735. [[DOI](https://doi.org/10.1001/archfami.2.7.729)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/8111497/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Arch%20Fam%20Med&title=A%20population-based%20study%20of%20health%20care-seeking%20behavior%20for%20treatment%20of%20urinary%20symptoms.%20The%20Olmsted%20County%20Study%20of%20Urinary%20Symptoms%20and%20Health%20Status%20Among%20Men&author=S.%20Jacobsen&author=H.%20Guess&author=L.%20Panser&author=C.%20Girman&author=C.%20Chute&volume=2&publication_year=1993&pages=729-735&pmid=8111497&doi=10.1001/archfami.2.7.729&)]
  39. Kang J., Min G., Son H., Kim H., Lee H. (2011) National-wide data on the treatment of BPH in Korea. Prostate Cancer Prostatic Dis 14: 243–247. [[DOI](https://doi.org/10.1038/pcan.2011.12)] [[PMC free article](/articles/PMC3157607/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21502967/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Prostate%20Cancer%20Prostatic%20Dis&title=National-wide%20data%20on%20the%20treatment%20of%20BPH%20in%20Korea&author=J.%20Kang&author=G.%20Min&author=H.%20Son&author=H.%20Kim&author=H.%20Lee&volume=14&publication_year=2011&pages=243-247&pmid=21502967&doi=10.1038/pcan.2011.12&)]
  40. Kawabe K., Yoshida M., Homma Y. (2006) Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int 98: 1019–1024. [[DOI](https://doi.org/10.1111/j.1464-410X.2006.06448.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16945121/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=Silodosin,%20a%20new%20alpha1A-adrenoceptor-selective%20antagonist%20for%20treating%20benign%20prostatic%20hyperplasia:%20results%20of%20a%20phase%20III%20randomized,%20placebo-controlled,%20double-blind%20study%20in%20Japanese%20men&author=K.%20Kawabe&author=M.%20Yoshida&author=Y.%20Homma&volume=98&publication_year=2006&pages=1019-1024&pmid=16945121&doi=10.1111/j.1464-410X.2006.06448.x&)]
  41. Kim S., Park J., Kim S., Lee S., Ahn T., Kim J., et al. (2011) Tadalafil administered once daily for treatment of lower urinary tract symptoms in Korean men with benign prostatic hyperplasia: results from a placebo-controlled pilot study using tamsulosin as an active control. LUTS 3: 86–93. [[DOI](https://doi.org/10.1111/j.1757-5672.2011.00088.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/26676392/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=LUTS&title=Tadalafil%20administered%20once%20daily%20for%20treatment%20of%20lower%20urinary%20tract%20symptoms%20in%20Korean%20men%20with%20benign%20prostatic%20hyperplasia:%20results%20from%20a%20placebo-controlled%20pilot%20study%20using%20tamsulosin%20as%20an%20active%20control&author=S.%20Kim&author=J.%20Park&author=S.%20Kim&author=S.%20Lee&author=T.%20Ahn&volume=3&publication_year=2011&pages=86-93&pmid=26676392&doi=10.1111/j.1757-5672.2011.00088.x&)]
  42. Kloner R., Jackson G., Emmick J., Mitchell M., Bedding A., Warner M., et al. (2004) Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. J Urol 172: 1935–1940. [[DOI](https://doi.org/10.1097/01.ju.0000142687.75577.e4)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/15540759/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Interaction%20between%20the%20phosphodiesterase%205%20inhibitor,%20tadalafil%20and%202%20alpha-blockers,%20doxazosin%20and%20tamsulosin%20in%20healthy%20normotensive%20men&author=R.%20Kloner&author=G.%20Jackson&author=J.%20Emmick&author=M.%20Mitchell&author=A.%20Bedding&volume=172&publication_year=2004&pages=1935-1940&pmid=15540759&doi=10.1097/01.ju.0000142687.75577.e4&)]
  43. Kojima M., Watanabe H., Watanabe M., Okihara K., Naya Y., Ukimura O. (1997) Preliminary results of power Doppler imaging in benign prostatic hyperplasia. Ultrasound Med Biol 23: 1305–1309. [[DOI](https://doi.org/10.1016/s0301-5629\(97\)00141-5)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9428128/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Ultrasound%20Med%20Biol&title=Preliminary%20results%20of%20power%20Doppler%20imaging%20in%20benign%20prostatic%20hyperplasia&author=M.%20Kojima&author=H.%20Watanabe&author=M.%20Watanabe&author=K.%20Okihara&author=Y.%20Naya&volume=23&publication_year=1997&pages=1305-1309&pmid=9428128&doi=10.1016/s0301-5629\(97\)00141-5&)]
  44. Kotera J., Fujishige K., Omori K. (2000) Immunohistochemical localization of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in rat tissues. J Histochem Cytochem 48: 685–693. [[DOI](https://doi.org/10.1177/002215540004800512)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10769052/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Histochem%20Cytochem&title=Immunohistochemical%20localization%20of%20cGMP-binding%20cGMP-specific%20phosphodiesterase%20\(PDE5\)%20in%20rat%20tissues&author=J.%20Kotera&author=K.%20Fujishige&author=K.%20Omori&volume=48&publication_year=2000&pages=685-693&pmid=10769052&doi=10.1177/002215540004800512&)]
  45. Lee E., Yoo K., Kim Y., Shin Y., Lee C. (1998) Prevalence of lower urinary tract symptoms in Korean men in a community-based study. Eur Urol 33: 17–21. [[DOI](https://doi.org/10.1159/000019529)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9471036/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Prevalence%20of%20lower%20urinary%20tract%20symptoms%20in%20Korean%20men%20in%20a%20community-based%20study&author=E.%20Lee&author=K.%20Yoo&author=Y.%20Kim&author=Y.%20Shin&author=C.%20Lee&volume=33&publication_year=1998&pages=17-21&pmid=9471036&doi=10.1159/000019529&)]
  46. Lee S., Paick J., Park H., Won J., Morisaki Y., Sorsaburu S., et al. (2014) The efficacy and safety of tadalafil 5 mg once daily in Korean men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: an integrated analysis. World J Mens Health 32: 28–35. [[DOI](https://doi.org/10.5534/wjmh.2014.32.1.28)] [[PMC free article](/articles/PMC4026231/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24872949/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=World%20J%20Mens%20Health&title=The%20efficacy%20and%20safety%20of%20tadalafil%205%20mg%20once%20daily%20in%20Korean%20men%20with%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia:%20an%20integrated%20analysis&author=S.%20Lee&author=J.%20Paick&author=H.%20Park&author=J.%20Won&author=Y.%20Morisaki&volume=32&publication_year=2014&pages=28-35&pmid=24872949&doi=10.5534/wjmh.2014.32.1.28&)]
  47. Li M., Garcia L., Rosen R. (2005) Lower urinary tract symptoms and male sexual dysfunction in Asia: a survey of ageing men from five Asian countries. BJU Int 96: 1339–1354. [[DOI](https://doi.org/10.1111/j.1464-410X.2005.05831.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16287456/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=Lower%20urinary%20tract%20symptoms%20and%20male%20sexual%20dysfunction%20in%20Asia:%20a%20survey%20of%20ageing%20men%20from%20five%20Asian%20countries&author=M.%20Li&author=L.%20Garcia&author=R.%20Rosen&volume=96&publication_year=2005&pages=1339-1354&pmid=16287456&doi=10.1111/j.1464-410X.2005.05831.x&)]
  48. Liguori G., Trombetta C., De Giorgi G., Pomara G., Maio G., Vecchio D., et al. (2009) Efficacy and safety of combined oral therapy with tadalafil and alfuzosin: an integrated approach to the management of patients with lower urinary tract symptoms and erectile dysfunction. Preliminary report. J Sex Med 6: 544–552. [[DOI](https://doi.org/10.1111/j.1743-6109.2008.01109.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19138360/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Efficacy%20and%20safety%20of%20combined%20oral%20therapy%20with%20tadalafil%20and%20alfuzosin:%20an%20integrated%20approach%20to%20the%20management%20of%20patients%20with%20lower%20urinary%20tract%20symptoms%20and%20erectile%20dysfunction.%20Preliminary%20report&author=G.%20Liguori&author=C.%20Trombetta&author=G.%20De%20Giorgi&author=G.%20Pomara&author=G.%20Maio&volume=6&publication_year=2009&pages=544-552&pmid=19138360&doi=10.1111/j.1743-6109.2008.01109.x&)]
  49. Loughney K., Hill T., Florio V., Uher L., Rosman G., Wolda S., et al. (1998) Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3′,5′-cyclic nucleotide phosphodiesterase. Gene 216: 139–147. [[DOI](https://doi.org/10.1016/s0378-1119\(98\)00303-5)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9714779/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Gene&title=Isolation%20and%20characterization%20of%20cDNAs%20encoding%20PDE5A,%20a%20human%20cGMP-binding,%20cGMP-specific%203%E2%80%B2,5%E2%80%B2-cyclic%20nucleotide%20phosphodiesterase&author=K.%20Loughney&author=T.%20Hill&author=V.%20Florio&author=L.%20Uher&author=G.%20Rosman&volume=216&publication_year=1998&pages=139-147&pmid=9714779&doi=10.1016/s0378-1119\(98\)00303-5&)]
  50. Mammi C., Pastore D., Lombardo M., Ferrelli F., Caprio M., Consoli C., et al. (2011) Sildenafil reduces insulin-resistance in human endothelial cells. PLoS One 6: e14542. [[DOI](https://doi.org/10.1371/journal.pone.0014542)] [[PMC free article](/articles/PMC3030559/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21297971/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=PLoS%20One&title=Sildenafil%20reduces%20insulin-resistance%20in%20human%20endothelial%20cells&author=C.%20Mammi&author=D.%20Pastore&author=M.%20Lombardo&author=F.%20Ferrelli&author=M.%20Caprio&volume=6&publication_year=2011&pages=e14542&pmid=21297971&doi=10.1371/journal.pone.0014542&)]
  51. McVary K., Roehrborn C., Kaminetsky J., Auerbach S., Wachs B., Young J., et al. (2007) Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 177: 1401–1407. [[DOI](https://doi.org/10.1016/j.juro.2006.11.037)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17382741/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Tadalafil%20relieves%20lower%20urinary%20tract%20symptoms%20secondary%20to%20benign%20prostatic%20hyperplasia&author=K.%20McVary&author=C.%20Roehrborn&author=J.%20Kaminetsky&author=S.%20Auerbach&author=B.%20Wachs&volume=177&publication_year=2007&pages=1401-1407&pmid=17382741&doi=10.1016/j.juro.2006.11.037&)]
  52. Minagawa T., Aizawa N., Igawa Y., Wyndaele J. (2012) Inhibitory effects of phosphodiesterase 5 inhibitor, tadalafil, on mechanosensitive bladder afferent nerve activities of the rat, and on acrolein-induced hyperactivity of these nerves. BJU Int 110: E259–E266. [[DOI](https://doi.org/10.1111/j.1464-410X.2012.11255.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22591258/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=Inhibitory%20effects%20of%20phosphodiesterase%205%20inhibitor,%20tadalafil,%20on%20mechanosensitive%20bladder%20afferent%20nerve%20activities%20of%20the%20rat,%20and%20on%20acrolein-induced%20hyperactivity%20of%20these%20nerves&author=T.%20Minagawa&author=N.%20Aizawa&author=Y.%20Igawa&author=J.%20Wyndaele&volume=110&publication_year=2012&pages=E259-E266&pmid=22591258&doi=10.1111/j.1464-410X.2012.11255.x&)]
  53. Morelli A., Filippi S., Comeglio P., Sarchielli E., Chavalmane A., Vignozzi L., et al. (2010) Acute vardenafil administration improves bladder oxygenation in spontaneously hypertensive rats. J Sex Med 7: 107–120. [[DOI](https://doi.org/10.1111/j.1743-6109.2009.01558.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19889145/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Acute%20vardenafil%20administration%20improves%20bladder%20oxygenation%20in%20spontaneously%20hypertensive%20rats&author=A.%20Morelli&author=S.%20Filippi&author=P.%20Comeglio&author=E.%20Sarchielli&author=A.%20Chavalmane&volume=7&publication_year=2010&pages=107-120&pmid=19889145&doi=10.1111/j.1743-6109.2009.01558.x&)]
  54. Morelli A., Sarchielli E., Comeglio P., Filippi S., Mancina R., Gacci M., et al. (2011a) Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats. J Sex Med 8: 2746–2760. [[DOI](https://doi.org/10.1111/j.1743-6109.2011.02416.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21812935/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Phosphodiesterase%20type%205%20expression%20in%20human%20and%20rat%20lower%20urinary%20tract%20tissues%20and%20the%20effect%20of%20tadalafil%20on%20prostate%20gland%20oxygenation%20in%20spontaneously%20hypertensive%20rats&author=A.%20Morelli&author=E.%20Sarchielli&author=P.%20Comeglio&author=S.%20Filippi&author=R.%20Mancina&volume=8&publication_year=2011a&pages=2746-2760&pmid=21812935&doi=10.1111/j.1743-6109.2011.02416.x&)]
  55. Morelli G., Pagni R., Mariani C., Minervini R., Morelli A., Gori F., et al. (2011b) Results of vardenafil mediated power Doppler ultrasound, contrast enhanced ultrasound and systematic random biopsies to detect prostate cancer. J Urol 185: 2126–2131. [[DOI](https://doi.org/10.1016/j.juro.2011.02.014)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21496853/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Results%20of%20vardenafil%20mediated%20power%20Doppler%20ultrasound,%20contrast%20enhanced%20ultrasound%20and%20systematic%20random%20biopsies%20to%20detect%20prostate%20cancer&author=G.%20Morelli&author=R.%20Pagni&author=C.%20Mariani&author=R.%20Minervini&author=A.%20Morelli&volume=185&publication_year=2011b&pages=2126-2131&pmid=21496853&doi=10.1016/j.juro.2011.02.014&)]
  56. Moul S., McVary K. (2010) Lower urinary tract symptoms, obesity and the metabolic syndrome. Curr Opin Urol 20: 7–12. [[DOI](https://doi.org/10.1097/MOU.0b013e3283336f3f)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19904208/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Curr%20Opin%20Urol&title=Lower%20urinary%20tract%20symptoms,%20obesity%20and%20the%20metabolic%20syndrome&author=S.%20Moul&author=K.%20McVary&volume=20&publication_year=2010&pages=7-12&pmid=19904208&doi=10.1097/MOU.0b013e3283336f3f&)]
  57. Musicki B., Bivalacqua T., Champion H., Burnett A. (2014) Sildenafil promotes eNOS activation and inhibits NADPH oxidase in the transgenic sickle cell mouse penis. J Sex Med 11: 424–430. [[DOI](https://doi.org/10.1111/jsm.12391)] [[PMC free article](/articles/PMC4011711/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24251665/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Sildenafil%20promotes%20eNOS%20activation%20and%20inhibits%20NADPH%20oxidase%20in%20the%20transgenic%20sickle%20cell%20mouse%20penis&author=B.%20Musicki&author=T.%20Bivalacqua&author=H.%20Champion&author=A.%20Burnett&volume=11&publication_year=2014&pages=424-430&pmid=24251665&doi=10.1111/jsm.12391&)]
  58. Nishizawa O., Yoshida M., Takeda M., Yokoyama O., Morisaki Y., Murakami M., et al. (2015) Tadalafil 5 mg once daily for the treatment of Asian men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: analyses of data pooled from three randomized, double-blind, placebo-controlled studies. Int J Urol 22: 378–384. [[DOI](https://doi.org/10.1111/iju.12699)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/25711404/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Urol&title=Tadalafil%205%20mg%20once%20daily%20for%20the%20treatment%20of%20Asian%20men%20with%20lower%20urinary%20tract%20symptoms%20secondary%20to%20benign%20prostatic%20hyperplasia:%20analyses%20of%20data%20pooled%20from%20three%20randomized,%20double-blind,%20placebo-controlled%20studies&author=O.%20Nishizawa&author=M.%20Yoshida&author=M.%20Takeda&author=O.%20Yokoyama&author=Y.%20Morisaki&volume=22&publication_year=2015&pages=378-384&pmid=25711404&doi=10.1111/iju.12699&)]
  59. Oelke M., Bachmann A., Descazeaud A., Emberton M., Gravas S., Michel M., et al. (2013) EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol 64: 118–140. [[DOI](https://doi.org/10.1016/j.eururo.2013.03.004)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/23541338/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=EAU%20guidelines%20on%20the%20treatment%20and%20follow-up%20of%20non-neurogenic%20male%20lower%20urinary%20tract%20symptoms%20including%20benign%20prostatic%20obstruction&author=M.%20Oelke&author=A.%20Bachmann&author=A.%20Descazeaud&author=M.%20Emberton&author=S.%20Gravas&volume=64&publication_year=2013&pages=118-140&pmid=23541338&doi=10.1016/j.eururo.2013.03.004&)]
  60. Oelke M., Giuliano F., Mirone V., Xu L., Cox D., Viktrup L. (2012) Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. Eur Urol 61: 917–925. [[DOI](https://doi.org/10.1016/j.eururo.2012.01.013)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22297243/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Monotherapy%20with%20tadalafil%20or%20tamsulosin%20similarly%20improved%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia%20in%20an%20international,%20randomised,%20parallel,%20placebo-controlled%20clinical%20trial&author=M.%20Oelke&author=F.%20Giuliano&author=V.%20Mirone&author=L.%20Xu&author=D.%20Cox&volume=61&publication_year=2012&pages=917-925&pmid=22297243&doi=10.1016/j.eururo.2012.01.013&)]
  61. Oelke M., Weiss J., Mamoulakis C., Cox D., Ruff D., Viktrup L. (2014) Effects of tadalafil on nighttime voiding (nocturia) in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a post hoc analysis of pooled data from four randomized, placebo-controlled clinical studies. World J Urol 32: 1127–1132. [[DOI](https://doi.org/10.1007/s00345-014-1255-z)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24504761/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=World%20J%20Urol&title=Effects%20of%20tadalafil%20on%20nighttime%20voiding%20\(nocturia\)%20in%20men%20with%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia:%20a%20post%20hoc%20analysis%20of%20pooled%20data%20from%20four%20randomized,%20placebo-controlled%20clinical%20studies&author=M.%20Oelke&author=J.%20Weiss&author=C.%20Mamoulakis&author=D.%20Cox&author=D.%20Ruff&volume=32&publication_year=2014&pages=1127-1132&pmid=24504761&doi=10.1007/s00345-014-1255-z&)]
  62. Ozden C., Gunay I., Deren T., Bulut S., Ozdal O., Koparal S., et al. (2010) Effect of transurethral resection of prostate on prostatic resistive index. Urol Int 84: 191–193. [[DOI](https://doi.org/10.1159/000277597)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/20215824/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Urol%20Int&title=Effect%20of%20transurethral%20resection%20of%20prostate%20on%20prostatic%20resistive%20index&author=C.%20Ozden&author=I.%20Gunay&author=T.%20Deren&author=S.%20Bulut&author=O.%20Ozdal&volume=84&publication_year=2010&pages=191-193&pmid=20215824&doi=10.1159/000277597&)]
  63. Park H., Park N. (2013) Combination therapy with dutasteride and tadalafil in men with moderate-to-severe benign prostatic hyperplasia. Eur Urol 12(Suppl): e1092. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Combination%20therapy%20with%20dutasteride%20and%20tadalafil%20in%20men%20with%20moderate-to-severe%20benign%20prostatic%20hyperplasia&author=H.%20Park&author=N.%20Park&volume=12&issue=Suppl&publication_year=2013&pages=e1092&)]
  64. Pinggera G., Frauscher F., Paduch D., Bolyakov A., Efros M., Kaminetsky J., et al. (2014) Effect of tadalafil once daily on prostate blood flow and perfusion in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: A randomized, double-blind, multicenter, placebo-controlled trial. Urology 84: 412–420. [[DOI](https://doi.org/10.1016/j.urology.2014.02.063)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24938580/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Urology&title=Effect%20of%20tadalafil%20once%20daily%20on%20prostate%20blood%20flow%20and%20perfusion%20in%20men%20with%20lower%20urinary%20tract%20symptoms%20secondary%20to%20benign%20prostatic%20hyperplasia:%20A%20randomized,%20double-blind,%20multicenter,%20placebo-controlled%20trial&author=G.%20Pinggera&author=F.%20Frauscher&author=D.%20Paduch&author=A.%20Bolyakov&author=M.%20Efros&volume=84&publication_year=2014&pages=412-420&pmid=24938580&doi=10.1016/j.urology.2014.02.063&)]
  65. Porst H., Kim E., Casabe A., Mirone V., Secrest R., Xu L., et al. (2011) Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: Results of an international randomized, double-blind, placebo-controlled trial. Eur Urol 60: 1105–1113. [[DOI](https://doi.org/10.1016/j.eururo.2011.08.005)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21871706/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Efficacy%20and%20safety%20of%20tadalafil%20once%20daily%20in%20the%20treatment%20of%20men%20with%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia:%20Results%20of%20an%20international%20randomized,%20double-blind,%20placebo-controlled%20trial&author=H.%20Porst&author=E.%20Kim&author=A.%20Casabe&author=V.%20Mirone&author=R.%20Secrest&volume=60&publication_year=2011&pages=1105-1113&pmid=21871706&doi=10.1016/j.eururo.2011.08.005&)]
  66. Porst H., Oelke M., Goldfischer E., Cox D., Watts S., Dey D., et al. (2013) Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: subgroup analyses of pooled data from 4 multinational, randomized, placebo-controlled clinical studies. Urology 82: 667–673. [[DOI](https://doi.org/10.1016/j.urology.2013.05.005)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/23876588/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Urology&title=Efficacy%20and%20safety%20of%20tadalafil%205%20mg%20once%20daily%20for%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia:%20subgroup%20analyses%20of%20pooled%20data%20from%204%20multinational,%20randomized,%20placebo-controlled%20clinical%20studies&author=H.%20Porst&author=M.%20Oelke&author=E.%20Goldfischer&author=D.%20Cox&author=S.%20Watts&volume=82&publication_year=2013&pages=667-673&pmid=23876588&doi=10.1016/j.urology.2013.05.005&)]
  67. Roehrborn C. (2008) Pathology of benign prostatic hyperplasia. Int J Impot Res 20(Suppl. 3): S11–S18. [[DOI](https://doi.org/10.1038/ijir.2008.55)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/19002119/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Impot%20Res&title=Pathology%20of%20benign%20prostatic%20hyperplasia&author=C.%20Roehrborn&volume=20&issue=Suppl.%203&publication_year=2008&pages=S11-S18&pmid=19002119&doi=10.1038/ijir.2008.55&)]
  68. Roehrborn C., Casabe A., Glina S., Sorsaburu S., Henneges C., Viktrup L. (2015) Treatment satisfaction and clinically meaningful improvement with tadalafil and finasteride coadministration in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: secondary results from a 6-month, randomized, double-blind study comparing finasteride plus tadalafil with finasteride plus placebo. Int J Urol. DOI: 10.1111/iju.12741. [[DOI](https://doi.org/10.1111/iju.12741)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/25827166/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Urol&title=Treatment%20satisfaction%20and%20clinically%20meaningful%20improvement%20with%20tadalafil%20and%20finasteride%20coadministration%20in%20men%20with%20lower%20urinary%20tract%20symptoms%20and%20prostatic%20enlargement%20secondary%20to%20benign%20prostatic%20hyperplasia:%20secondary%20results%20from%20a%206-month,%20randomized,%20double-blind%20study%20comparing%20finasteride%20plus%20tadalafil%20with%20finasteride%20plus%20placebo&author=C.%20Roehrborn&author=A.%20Casabe&author=S.%20Glina&author=S.%20Sorsaburu&author=C.%20Henneges&publication_year=2015&pmid=25827166&doi=10.1111/iju.12741&)]
  69. Roehrborn C., Chapple C., Oelke M., Cox D., Esler A., Viktrup L. (2014) Effects of tadalafil once daily on maximum urinary flow rate in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. J Urol 191: 1045–1050. [[DOI](https://doi.org/10.1016/j.juro.2013.10.074)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24445278/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Effects%20of%20tadalafil%20once%20daily%20on%20maximum%20urinary%20flow%20rate%20in%20men%20with%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia&author=C.%20Roehrborn&author=C.%20Chapple&author=M.%20Oelke&author=D.%20Cox&author=A.%20Esler&volume=191&publication_year=2014&pages=1045-1050&pmid=24445278&doi=10.1016/j.juro.2013.10.074&)]
  70. Roehrborn C., McVary K., Elion-Mboussa A., Viktrup L. (2008) Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. J Urol 180: 1228–1234. [[DOI](https://doi.org/10.1016/j.juro.2008.06.079)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18722631/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Tadalafil%20administered%20once%20daily%20for%20lower%20urinary%20tract%20symptoms%20secondary%20to%20benign%20prostatic%20hyperplasia:%20a%20dose%20finding%20study&author=C.%20Roehrborn&author=K.%20McVary&author=A.%20Elion-Mboussa&author=L.%20Viktrup&volume=180&publication_year=2008&pages=1228-1234&pmid=18722631&doi=10.1016/j.juro.2008.06.079&)]
  71. Rosano G., Aversa A., Vitale C., Fabbri A., Fini M., Spera G. (2005) Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol 47: 214–220. [[DOI](https://doi.org/10.1016/j.eururo.2004.10.002)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/15661417/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Chronic%20treatment%20with%20tadalafil%20improves%20endothelial%20function%20in%20men%20with%20increased%20cardiovascular%20risk&author=G.%20Rosano&author=A.%20Aversa&author=C.%20Vitale&author=A.%20Fabbri&author=M.%20Fini&volume=47&publication_year=2005&pages=214-220.&pmid=15661417&doi=10.1016/j.eururo.2004.10.002&)]
  72. Rosen R., Altwein J., Boyle P., Kirby R., Lukacs B., Meuleman E., et al. (2003) Lower urinary tract symptoms and male sexual dysfunction: The multinational survey of the aging male (MSAM-7). Eur Urol 44: 637–649. [[DOI](https://doi.org/10.1016/j.eururo.2003.08.015)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/14644114/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Lower%20urinary%20tract%20symptoms%20and%20male%20sexual%20dysfunction:%20The%20multinational%20survey%20of%20the%20aging%20male%20\(MSAM-7\)&author=R.%20Rosen&author=J.%20Altwein&author=P.%20Boyle&author=R.%20Kirby&author=B.%20Lukacs&volume=44&publication_year=2003&pages=637-649&pmid=14644114&doi=10.1016/j.eururo.2003.08.015&)]
  73. Rybalkin S., Bornfeldt K. (1999) Cyclic nucleotide phosphodiesterases and human arterial smooth muscle cell proliferation. Thromb Haemost 82: 424–434. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10605733/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Thromb%20Haemost&title=Cyclic%20nucleotide%20phosphodiesterases%20and%20human%20arterial%20smooth%20muscle%20cell%20proliferation&author=S.%20Rybalkin&author=K.%20Bornfeldt&volume=82&publication_year=1999&pages=424-434&pmid=10605733&)]
  74. Singh D., Mete U., Mandal A., Singh S. (2014) A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil _versus_. tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. J Sex Med 11: 187–196. [[DOI](https://doi.org/10.1111/jsm.12357)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24165272/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=A%20comparative%20randomized%20prospective%20study%20to%20evaluate%20efficacy%20and%20safety%20of%20combination%20of%20tamsulosin%20and%20tadalafil%20versus.%20tamsulosin%20or%20tadalafil%20alone%20in%20patients%20with%20lower%20urinary%20tract%20symptoms%20due%20to%20benign%20prostatic%20hyperplasia&author=D.%20Singh&author=U.%20Mete&author=A.%20Mandal&author=S.%20Singh&volume=11&publication_year=2014&pages=187-196&pmid=24165272&doi=10.1111/jsm.12357&)]
  75. Taher A., Meyer M., Stief C., Jonas U., Forssmann W. (1997) Cyclic nucleotide phosphodiesterase in human cavernous smooth muscle. World J Urol 15: 32–35. [[DOI](https://doi.org/10.1007/BF01275154)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/9066092/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=World%20J%20Urol&title=Cyclic%20nucleotide%20phosphodiesterase%20in%20human%20cavernous%20smooth%20muscle&author=A.%20Taher&author=M.%20Meyer&author=C.%20Stief&author=U.%20Jonas&author=W.%20Forssmann&volume=15&publication_year=1997&pages=32-35&pmid=9066092&doi=10.1007/BF01275154&)]
  76. Takeda M., Nishizawa O., Imaoka T., Maikuma H., Morisaki Y., Viktrup L. (2012) Tadalafil for the treatment of lower urinary tract symptoms in Japanese men with benign prostatic hyperplasia: results from a 12-week placebo-controlled dose-finding study with a 42-week open-label extension LUTS 4: 110–119. [[DOI](https://doi.org/10.1111/j.1757-5672.2012.00144.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/26676616/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=LUTS&title=Tadalafil%20for%20the%20treatment%20of%20lower%20urinary%20tract%20symptoms%20in%20Japanese%20men%20with%20benign%20prostatic%20hyperplasia:%20results%20from%20a%2012-week%20placebo-controlled%20dose-finding%20study%20with%20a%2042-week%20open-label%20extension&author=M.%20Takeda&author=O.%20Nishizawa&author=T.%20Imaoka&author=H.%20Maikuma&author=Y.%20Morisaki&volume=4&publication_year=2012&pages=110-119&pmid=26676616&doi=10.1111/j.1757-5672.2012.00144.x&)]
  77. Takeda M., Tang R., Shapiro E., Burnett A., Lepor H. (1995) Effects of nitric oxide on human and canine prostates. Urology 45: 440–446. [[DOI](https://doi.org/10.1016/S0090-4295\(99\)80013-2)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/7879335/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Urology&title=Effects%20of%20nitric%20oxide%20on%20human%20and%20canine%20prostates&author=M.%20Takeda&author=R.%20Tang&author=E.%20Shapiro&author=A.%20Burnett&author=H.%20Lepor&volume=45&publication_year=1995&pages=440-446&pmid=7879335&doi=10.1016/S0090-4295\(99\)80013-2&)]
  78. Takeda M., Yokoyama O., Lee S., Murakami M., Morisaki Y., Viktrup L. (2014) Tadalafil 5 mg once-daily therapy for men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results from a randomized, double-blind, placebo-controlled trial carried out in Japan and Korea. Int J Urol 21: 670–675. [[DOI](https://doi.org/10.1111/iju.12410)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/24571205/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Urol&title=Tadalafil%205%20mg%20once-daily%20therapy%20for%20men%20with%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia:%20results%20from%20a%20randomized,%20double-blind,%20placebo-controlled%20trial%20carried%20out%20in%20Japan%20and%20Korea&author=M.%20Takeda&author=O.%20Yokoyama&author=S.%20Lee&author=M.%20Murakami&author=Y.%20Morisaki&volume=21&publication_year=2014&pages=670-675&pmid=24571205&doi=10.1111/iju.12410&)]
  79. Terai A., Kakehi Y., Terachi T., Ogawa O. (2000) National trend of management of benign prostatic hyperplasia in Japan during 1990s: analysis of national health statistics. Hinyokika Kiyo 46: 537–544. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11019372/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Hinyokika%20Kiyo&title=National%20trend%20of%20management%20of%20benign%20prostatic%20hyperplasia%20in%20Japan%20during%201990s:%20analysis%20of%20national%20health%20statistics&author=A.%20Terai&author=Y.%20Kakehi&author=T.%20Terachi&author=O.%20Ogawa&volume=46&publication_year=2000&pages=537-544&pmid=11019372&)]
  80. Traish A., Hassani J., Guay A., Zitzmann M., Hansen M. (2011) Adverse side effects of 5alpha-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J Sex Med 8: 872–884. [[DOI](https://doi.org/10.1111/j.1743-6109.2010.02157.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/21176115/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Sex%20Med&title=Adverse%20side%20effects%20of%205alpha-reductase%20inhibitors%20therapy:%20persistent%20diminished%20libido%20and%20erectile%20dysfunction%20and%20depression%20in%20a%20subset%20of%20patients&author=A.%20Traish&author=J.%20Hassani&author=A.%20Guay&author=M.%20Zitzmann&author=M.%20Hansen&volume=8&publication_year=2011&pages=872-884&pmid=21176115&doi=10.1111/j.1743-6109.2010.02157.x&)]
  81. Tsukamoto T., Kumamoto Y., Masumori N., Miyake H., Rhodes T., Girman C., et al. (1995) Prevalence of prostatism in Japanese men in a community-based study with comparison to a similar American study. J Urol 154: 391–395. [[DOI](https://doi.org/10.1097/00005392-199508000-00018)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/7541852/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Prevalence%20of%20prostatism%20in%20Japanese%20men%20in%20a%20community-based%20study%20with%20comparison%20to%20a%20similar%20American%20study&author=T.%20Tsukamoto&author=Y.%20Kumamoto&author=N.%20Masumori&author=H.%20Miyake&author=T.%20Rhodes&volume=154&publication_year=1995&pages=391-395&pmid=7541852&doi=10.1097/00005392-199508000-00018&)]
  82. Tsuru N., Kurita Y., Masuda H., Suzuki K., Fujita K. (2002) Role of Doppler ultrasound and resistive index in benign prostatic hypertrophy. Int J Urol 9: 427–430. [[DOI](https://doi.org/10.1046/j.1442-2042.2002.00494.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/12225338/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Urol&title=Role%20of%20Doppler%20ultrasound%20and%20resistive%20index%20in%20benign%20prostatic%20hypertrophy&author=N.%20Tsuru&author=Y.%20Kurita&author=H.%20Masuda&author=K.%20Suzuki&author=K.%20Fujita&volume=9&publication_year=2002&pages=427-430&pmid=12225338&doi=10.1046/j.1442-2042.2002.00494.x&)]
  83. Uckert S., Kuthe A., Jonas U., Stief C. (2001) Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol 166: 2484–2490. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11696815/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Characterization%20and%20functional%20relevance%20of%20cyclic%20nucleotide%20phosphodiesterase%20isoenzymes%20of%20the%20human%20prostate&author=S.%20Uckert&author=A.%20Kuthe&author=U.%20Jonas&author=C.%20Stief&volume=166&publication_year=2001&pages=2484-2490&pmid=11696815&)]
  84. Uckert S., Sormes M., Kedia G., Scheller F., Knapp W., Jonas U., et al. (2008) Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue. Urology 71: 526–530. [[DOI](https://doi.org/10.1016/j.urology.2007.10.051)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18342202/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Urology&title=Effects%20of%20phosphodiesterase%20inhibitors%20on%20tension%20induced%20by%20norepinephrine%20and%20accumulation%20of%20cyclic%20nucleotides%20in%20isolated%20human%20prostatic%20tissue&author=S.%20Uckert&author=M.%20Sormes&author=G.%20Kedia&author=F.%20Scheller&author=W.%20Knapp&volume=71&publication_year=2008&pages=526-530&pmid=18342202&doi=10.1016/j.urology.2007.10.051&)]
  85. Verhamme K., Dieleman J., Bleumink G., Van Der Lei J., Sturkenboom M., Artibani W., et al. (2002) Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care–the Triumph project. Eur Urol 42: 323–328. [[DOI](https://doi.org/10.1016/s0302-2838\(02\)00354-8)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/12361895/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Incidence%20and%20prevalence%20of%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia%20in%20primary%20care%E2%80%93the%20Triumph%20project&author=K.%20Verhamme&author=J.%20Dieleman&author=G.%20Bleumink&author=J.%20Van%20Der%20Lei&author=M.%20Sturkenboom&volume=42&publication_year=2002&pages=323-328&pmid=12361895&doi=10.1016/s0302-2838\(02\)00354-8&)]
  86. Waldkirch E., Uckert S., Langnase K., Richter K., Jonas U., Wolf G., et al. (2007) Immunohistochemical distribution of cyclic GMP-dependent protein kinase-1 in human prostate tissue. Eur Urol 52: 495–501. [[DOI](https://doi.org/10.1016/j.eururo.2007.02.004)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/17329019/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Eur%20Urol&title=Immunohistochemical%20distribution%20of%20cyclic%20GMP-dependent%20protein%20kinase-1%20in%20human%20prostate%20tissue&author=E.%20Waldkirch&author=S.%20Uckert&author=K.%20Langnase&author=K.%20Richter&author=U.%20Jonas&volume=52&publication_year=2007&pages=495-501&pmid=17329019&doi=10.1016/j.eururo.2007.02.004&)]
  87. Watkins C., Sawa A., Jaffrey S., Blackshaw S., Barrow R., Snyder S., et al. (2000) Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy. J Clin Invest 106: 373–384. [[DOI](https://doi.org/10.1172/JCI8273)] [[PMC free article](/articles/PMC314323/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10930440/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Clin%20Invest&title=Insulin%20restores%20neuronal%20nitric%20oxide%20synthase%20expression%20and%20function%20that%20is%20lost%20in%20diabetic%20gastropathy&author=C.%20Watkins&author=A.%20Sawa&author=S.%20Jaffrey&author=S.%20Blackshaw&author=R.%20Barrow&volume=106&publication_year=2000&pages=373-384&pmid=10930440&doi=10.1172/JCI8273&)]
  88. Wei J., Calhoun E., Jacobsen S. (2008) Urologic diseases in america project: benign prostatic hyperplasia. J Urol 179: S75–S80. [[DOI](https://doi.org/10.1016/j.juro.2008.03.141)] [[PMC free article](/articles/PMC11160437/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/18405761/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Urologic%20diseases%20in%20america%20project:%20benign%20prostatic%20hyperplasia&author=J.%20Wei&author=E.%20Calhoun&author=S.%20Jacobsen&volume=179&publication_year=2008&pages=S75-S80&pmid=18405761&doi=10.1016/j.juro.2008.03.141&)]
  89. Werkstrom V., Svensson A., Andersson K., Hedlund P. (2006) Phosphodiesterase 5 in the female pig and human urethra: morphological and functional aspects. BJU Int 98: 414–423. [[DOI](https://doi.org/10.1111/j.1464-410X.2006.06217.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/16626307/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=BJU%20Int&title=Phosphodiesterase%205%20in%20the%20female%20pig%20and%20human%20urethra:%20morphological%20and%20functional%20aspects&author=V.%20Werkstrom&author=A.%20Svensson&author=K.%20Andersson&author=P.%20Hedlund&volume=98&publication_year=2006&pages=414-423&pmid=16626307&doi=10.1111/j.1464-410X.2006.06217.x&)]
  90. Yokoyama O., Yoshida M., Kim S., Wang C., Imaoka T., Morisaki Y., et al. (2013) Tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: A randomized placebo- and tamsulosin-controlled 12-week study in Asian men. Int J Urol 20: 193–201. [[DOI](https://doi.org/10.1111/j.1442-2042.2012.03130.x)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22958078/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Int%20J%20Urol&title=Tadalafil%20once%20daily%20for%20lower%20urinary%20tract%20symptoms%20suggestive%20of%20benign%20prostatic%20hyperplasia:%20A%20randomized%20placebo-%20and%20tamsulosin-controlled%2012-week%20study%20in%20Asian%20men&author=O.%20Yokoyama&author=M.%20Yoshida&author=S.%20Kim&author=C.%20Wang&author=T.%20Imaoka&volume=20&publication_year=2013&pages=193-201&pmid=22958078&doi=10.1111/j.1442-2042.2012.03130.x&)]
  91. Zenzmaier C., Kern J., Sampson N., Heitz M., Plas E., Untergasser G., et al. (2012) Phosphodiesterase type 5 inhibition reverts prostate fibroblast-to-myofibroblast trans-differentiation. Endocrinology 153: 5546–5555. [[DOI](https://doi.org/10.1210/en.2012-1431)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22948216/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Endocrinology&title=Phosphodiesterase%20type%205%20inhibition%20reverts%20prostate%20fibroblast-to-myofibroblast%20trans-differentiation&author=C.%20Zenzmaier&author=J.%20Kern&author=N.%20Sampson&author=M.%20Heitz&author=E.%20Plas&volume=153&publication_year=2012&pages=5546-5555&pmid=22948216&doi=10.1210/en.2012-1431&)]
  92. Zhang X., Li G., Wei X., Mo X., Hu L., Zha Y., et al. (2012) Resistive index of prostate capsular arteries: a newly identified parameter to diagnose and assess bladder outlet obstruction in patients with benign prostatic hyperplasia. J Urol 188: 881–887. [[DOI](https://doi.org/10.1016/j.juro.2012.04.114)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/22819411/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Urol&title=Resistive%20index%20of%20prostate%20capsular%20arteries:%20a%20newly%20identified%20parameter%20to%20diagnose%20and%20assess%20bladder%20outlet%20obstruction%20in%20patients%20with%20benign%20prostatic%20hyperplasia&author=X.%20Zhang&author=G.%20Li&author=X.%20Wei&author=X.%20Mo&author=L.%20Hu&volume=188&publication_year=2012&pages=881-887&pmid=22819411&doi=10.1016/j.juro.2012.04.114&)]



* * *

Articles from Therapeutic Advances in Urology are provided here courtesy of **SAGE Publications**

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

## ACTIONS

  * [ View on publisher site ](https://doi.org/10.1177/1756287215589238)
  * [ PDF (1.2 MB) ](pdf/10.1177_1756287215589238.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


