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Adults with obesity without diabetes received once-weekly subcutaneous retatrutide (4 mg, 9 mg, or 12 mg) or placebo for 80 weeks. Primary outcomes assessed weight change and pain in knee osteoarthritis, and apnea–hypopnea index in obstructive sleep apnea, using prespecified estimands. Results showed significantly greater weight loss and clinical improvements, with gastrointestinal effects as the most common adverse events.",{"@graph":69,"@context":123},[70,84,106],{"@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/retatrutide-a-triple-hormone-receptor-agonist-for-treatment-of-obesity-phase-3-randomized-trial/487537/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/retatrutide-a-triple-hormone-receptor-agonist-for-treatment-of-obesity-phase-3-randomized-trial/487537.png","ImageObject",300,407,{"name":92,"@type":93},"LangkahRina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-11","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",67,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What was the study design and treatment regimen for retatrutide?","Question",{"text":113,"@type":114},"The study was a phase 3, randomized, double-blind, placebo-controlled trial. Participants with obesity without diabetes received once-weekly subcutaneous injections of retatrutide (4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What primary outcomes were evaluated?",{"text":118,"@type":114},"Primary outcomes included percent change in body weight and change in the WOMAC pain score for participants with knee osteoarthritis, and change in the apnea–hypopnea index for participants with obstructive sleep apnea.",{"name":120,"@type":111,"acceptedAnswer":121},"What were the main efficacy and safety findings?",{"text":122,"@type":114},"Retatrutide produced significant weight reduction, reduced pain in knee osteoarthritis, and reduced apnea–hypopnea events in obstructive sleep apnea. The most common adverse events were gastrointestinal.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},487537,1790878100,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","The new e ngla nd jou r na l of m e dicine  \nOriginal Article  \nRetatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity  \nAnia M. Jastreboff, M. D., Ph. D.,1-3 Lee M. Kaplan, M. D., Ph. D.,4 Melanie J. Davies, M.D.,5,6John P.H. Wilding, M.D.,7 Nadia N. Ahmad, M.D., M.P.H.,8 Megan Murray, Ph. D.,8 Yu Du, Ph. D.,8 Nune Makarova, M. D., M. P. H.,8 Kathryn Giblin, M. D.,8 Nanette C. Schloot, M. D.,8 and Yan Wang, M. D., Ph. D.,8 for the TRIUMPH-1 Investigators*  \nA BST RACT  \nBACKGROUND  \nRetatrutide is a triple-receptor agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors.  \nMETHODS  \nIn this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks. Primary outcomes (evaluated in the 9-mg and 12-mg groups each vs. placebo) were the percent change in body weight and the change in the WOMAC pain score (ranging from 1 to 10, with higher scores indicating worse pain) in the subgroup of 574 participants with knee osteoarthritis and the change in the apnea–hypopnea index in the 243 participants with obstructive sleep apnea. For weight-related end points, intercurrent events were handled by a treatment-regimen estimand (intention-to-treat [ITT]). For end points in participants with knee osteoarthritis or obstructive sleep apnea, a hybrid-treatment estimand was applied, with a hypothetical strategy for intercurrent events suggesting treatment failure; ITT results are also reported.  \nRESULTS  \nA total of 2339 participants underwent randomization. The mean percent change in body weight in the retatrutide groups was −17.6%(4-mg dose), −23.7%(9-mg dose), and −25.0%(12-mg dose) versus −3.9% in the placebo group (differences, −19.8 and −21.0 percentage points, respectively; P\u003C0.001 for both comparisons). Among the participants with knee osteoarthritis, the corresponding changes in the pain score in the retatrutide groups for the hybrid estimand were −3.2, −3.5, and −3.6 versus −1.9 with placebo (differences, −1.6 and −1.8 points; both P\u003C0.001); the corresponding changes for the ITT estimand were −3.4, −3.9, and −4.1 versus −2.5 with placebo (differences, −1.4 and −1.6 points; both P\u003C0.001). Among the participants with obstructive sleep apnea, the corresponding changes in events per hour in theretatrutide groups for the hybrid-treatment estimand were −22.9, −34.3, and 31.7 versus −9.9 (differences, −24.4 and −21.9; both P\u003C0.001); the corresponding changes for the ITT estimand were −22.8, −34.3, and −32.1 versus −9.6 (differences, −24.7 and −22.5; both P\u003C0.001). The most common adverse events were gastrointestinal.  \nCONCLUSIONS  \nIn adults with obesity, retatrutide resulted in significant weight reduction, reduced pain in participants with knee osteoarthritis, and reduced apnea–hypopnea events in participants with obstructive sleep apnea. (Funded by Eli Lilly; TRIUMPH-1 [ClinicalTrials.gov](ClinicalTrials.gov) number, NCT05929066.)  \nAuthor affiliations are listed at the end of the article. Ania M. Jastreboff can be contacted at [ania.jastreboff@yale.edu](ania.jastreboff@yale.edu) or at Yale University School of Medicine, Endocrinology and Metabolism, 333 Cedar St., New Haven, CT 06520.  \n*A list of the investigators in the  \nTRIUMPH-1 trial is provided in the Supplementary Appendix, available at [NEJM.org](NEJM.org).  \nNanette C. Schloot and Yan Wang contributed equally to this article.  \nThis article was published on September 29, 2026, [at NEJM.org](at NEJM.org).  \nDOI: 10.1056/NEJMoa2604169  \nCopyright © 2026 Massachusetts Medical Society.  \nn eng l j med  \n[nej m.org](nej m.org)  \n1  \nThe new e ngla nd jou r na l of m e dicine  \nO besity, the most prevalent chron  \nic disease of our time, affects the health  \nof more than 1 billion people worldwide.1 Nutrient-stimulated hormone receptor modulators2—including the mono-","cbCaittZnsxLbHNg","https://ap.wps.com/l/cbCaittZnsxLbHNg","pdf",207683,13,"English","# Abstract\n# Background\n# Methods\n## Trial Design and Data Monitoring\n# Results\n# Conclusions","[{\"question\":\"What was the study design and treatment regimen for retatrutide?\",\"answer\":\"The study was a phase 3, randomized, double-blind, placebo-controlled trial. Participants with obesity without diabetes received once-weekly subcutaneous injections of retatrutide (4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.\"},{\"question\":\"What primary outcomes were evaluated?\",\"answer\":\"Primary outcomes included percent change in body weight and change in the WOMAC pain score for participants with knee osteoarthritis, and change in the apnea–hypopnea index for participants with obstructive sleep apnea.\"},{\"question\":\"What were the main efficacy and safety findings?\",\"answer\":\"Retatrutide produced significant weight reduction, reduced pain in knee osteoarthritis, and reduced apnea–hypopnea events in obstructive sleep apnea. The most common adverse events were gastrointestinal.\"}]","Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity - Phase 3 Randomized Trial | PDF",1790808688,33]