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Lifestyle remains central, while GLP-1 receptor agonists are highlighted as effective pharmacotherapies. Evidence from recent studies and meta-analyses is discussed to support tirzepatide’s superior efficacy versus semaglutide in weight loss, HbA1c reduction, waist circumference changes, and lipid profile improvements, with a broadly comparable adverse-event profile. Remaining uncertainty concerns long-term cardiovascular, psychiatric, and ophthalmic safety and limited head-to-head dose-matched trials.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/pharmacological-progress-in-obesity-tirzepatides-rising-advantage-over-semaglutide-letter-to-the-editor/435640/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/pharmacological-progress-in-obesity-tirzepatides-rising-advantage-over-semaglutide-letter-to-the-editor/435640.png","ImageObject",300,407,{"name":92,"@type":93},"mieayamfan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-29",true,{"@type":101,"interactionType":102,"userInteractionCount":81},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What clinical problem does the letter address?","Question",{"text":111,"@type":112},"It addresses obesity as a widespread chronic condition associated with increased morbidity and mortality, including higher risk of type 2 diabetes and cardiovascular disease.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"What evidence does the letter cite for tirzepatide’s advantage?",{"text":116,"@type":112},"It cites a New England Journal of Medicine study, real-world data from JAMA, and a meta-analysis showing greater weight loss and HbA1c reductions with tirzepatide compared with semaglutide.",{"name":118,"@type":109,"acceptedAnswer":119},"Are there uncertainties about long-term safety or direct comparisons?",{"text":120,"@type":112},"Yes. Long-term cardiovascular, psychiatric, and ophthalmic safety data are described as limited for both agents, and the lack of direct dose-matched head-to-head trials limits definitive comparisons.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},435640,1790688459,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":138,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":67,"update_tm":142,"read_time":24},962090893677,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Letter to the Editor  \nPharmacological progress in obesity: tirzepatide’s rising advantage over semaglutide  \nSohrab Khan, MBBSa , Haris Afridi, MBBSb , Raghabendra Kumar Mahato, MBBSc ,*, Muhammad Zubair, MBBSb , Umaid Khan, MBBSb , Sana Ullah, MBBSb  \nDear Editor,  \nOverweight and obesity are widespread, chronic, relapsing, and progressive conditions strongly associated with increased morbidity and mortality worldwide[1] . They significantly elevate the risk of complications such as type 2 diabetes and cardiovascular disease. While lifestyle interventions remain the cornerstone of obesity management, glucagon-like peptide-1 (GLP-1) receptor agonists and their analogues have emerged as effective pharmacotherapies. Semaglutide, a GLP-1 analogue, has long demonstrated efficacy for weight loss in both diabetic and non-diabetic individuals with obesity. However, the recently approved tirzepatide – a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist – has shown superior efficacy.  \nA recent study published in the New England Journal of Medicine reported that tirzepatide leads to greater weight loss and more significant reductions in waist circumference compared to semaglutide, highlighting its enhanced effectiveness in obesity management[2] . Supporting these findings, real-world data published in JAMA demonstrated that participants with obesity but without diabetes who were treated with tirzepatide experienced more substantial and sustained weight loss at 3, 6, and 12 months compared to those receiving semaglutide [3] . These outcomes reinforce tirzepatide’s superior performance in both short-and long-term weight reduction.  \nFurther validation comes from a meta-analysis showing that subcutaneous tirzepatide produces greater reductions in HbA1cand body weight than semaglutide in patients with type 2 diabetes[4] . Additionally, patients treated with tirzepatide exhibited lower triglyceride and serum very-low-density lipoprotein  \naDepartment of Medicine, Gujranwala Medical College, Gujranwala, Pakistan, bDepartment of Medicine, Gujranwala Medical College, Gujranwala, Pakistan and cDepartment of Medicine, Gandaki Medical College Teaching Hospital and Research Centre, Pokhara, Nepal  \nSponsorships or competing interests that may be relevant to the content are disclosed at the end of this article.  \n*Corresponding author. Address: Department of Medicine, Gandaki Medical College Teaching Hospital and Research Centre, Pokhara 33700, Nepal. Tel.: +[977-9745829807. E-mail: raghabendra.mahato2024@gmcthrc.edu](977-9745829807. E-mail: raghabendra.mahato2024@gmcthrc.edu)[ ](977-9745829807. E-mail: raghabendra.mahato2024@gmcthrc.edu)(R. K. Mahato).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.  \nAnnals of Medicine & Surgery (2026) 88:1110–1111  \nReceived 20 November 2025; Accepted 21 November 2025  \nPublished online 3 December 2025  \n[http://dx.doi.org/10.1097/MS9.0000000000004507](http://dx.doi.org/10.1097/MS9.0000000000004507)  \n(VLDL) levels, alongside higher high-density lipoprotein (HDL) cholesterol levels compared to those treated with semaglutide[5] .  \nCollectively, these studies indicate that tirzepatide offers significantly greater reductions in body weight and HbA1c, with an improved lipid profile, while maintaining a comparable adverse event profile to semaglutide. However, long-term data on cardiovascular, psychiatric, and ophthalmic safety remain limited for both agents. Evidence in special populations is also scarce, and the absence of direct, dose-matched head-to-head trials limits the ability to draw definitive comparisons, highlighting t","cbCaisfW1o5RILvE","https://ap.wps.com/l/cbCaisfW1o5RILvE","pdf",164265,"English","# Letter to the Editor\n## Background: obesity burden and treatment focus\n## Comparative evidence: tirzepatide vs semaglutide\n## Clinical outcomes: weight loss, HbA1c, lipid profile\n## Limitations and need for further research\n## AI transparency and ethical statements","[{\"question\":\"What clinical problem does the letter address?\",\"answer\":\"It addresses obesity as a widespread chronic condition associated with increased morbidity and mortality, including higher risk of type 2 diabetes and cardiovascular disease.\"},{\"question\":\"What evidence does the letter cite for tirzepatide’s advantage?\",\"answer\":\"It cites a New England Journal of Medicine study, real-world data from JAMA, and a meta-analysis showing greater weight loss and HbA1c reductions with tirzepatide compared with semaglutide.\"},{\"question\":\"Are there uncertainties about long-term safety or direct comparisons?\",\"answer\":\"Yes. Long-term cardiovascular, psychiatric, and ophthalmic safety data are described as limited for both agents, and the lack of direct dose-matched head-to-head trials limits definitive comparisons.\"}]","Pharmacological progress in obesity - Tirzepatide’s rising advantage over semaglutide - Letter to the Editor | PDF",1790674491]