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In this double-blind, placebo-controlled phase 2, trial, 507 adults with obesity (body mass index \u226530\u2009kg\u2009m\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>2<\/jats:sup>\n                    or \u226527\u2009kg\u2009m\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>2<\/jats:sup>\n                    with at least one obesity-associated complication (excluding diabetes) were randomized to nine groups (1:1:1:1:1:1:1:1:1 ratio) to receive treatment for 48\u2009weeks: placebo, bimagrumab (10\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    or 30\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    intravenously every 12\u2009weeks), semaglutide (1.0\u2009mg or 2.4\u2009mg subcutaneously once a week) and combinations thereof. An open-label treatment extension to week 72 followed. Randomization was stratified by sex across the treatment groups. The primary and secondary endpoints were absolute change from baseline in body weight at week 48 and week 72, respectively. The least squares mean absolute changes in body weight at week 48 were \u22129.3\u2009kg (bimagrumab 30\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), \u221214.2\u2009kg (semaglutide 2.4\u2009mg) and \u221217.8\u2009kg (bimagrumab 30\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    plus semaglutide 2.4\u2009mg\u2014that is, high-dose combination) versus \u22123.3\u2009kg (placebo) (all\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001 versus placebo). Continued improvements were observed through week 72. Common adverse events for bimagrumab included muscle spasms, diarrhea and acne, and semaglutide was associated with nausea, diarrhea, constipation and fatigue. Bimagrumab plus semaglutide resulted in substantial reductions in body weight, and safety was consistent with the known safety profiles of both drugs. ClinicalTrials.gov identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/study\/NCT05616013\" ext-link-type=\"uri\">NCT05616013<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04204-0","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:03:44Z","timestamp":1772445824000},"page":"869-882","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1127-9425","authenticated-orcid":false,"given":"Steven B.","family":"Heymsfield","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9890-9401","authenticated-orcid":false,"given":"Louis J.","family":"Aronne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope","family":"Montgomery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd B.","family":"Klickstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Dole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Mindeholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0477-3305","authenticated-orcid":false,"given":"Susan","family":"Spruill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Attie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the BELIEVE trial investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"4204_CR1","unstructured":"World Obesity Federation. 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It is now available under a Creative Commons Attribution 4.0 International license, CC-BY, \u00a9 The Author(s). The error has been corrected in the online version of the article.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.B.H. has a contract with Eli Lilly and Company for clinical trials (institutional support). He has received honoraria for serving on the medical advisory boards of Tanita Corporation, Novo Nordisk, Lilly, Regeneron, Abbott and Medifast. He is also on the Data Safety Monitoring Committee for Novo Nordisk. L.J.A. has received research funding from Lilly, Novo Nordisk, Altimmune and Skye Bioscience. He is a consultant\/advisory board member for Boehringer Ingelheim, Currax Pharmaceuticals, Lilly, Altimmune, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Pfizer, Veru Pharmaceuticals, Zealand Pharmaceuticals and Amgen. He has received payments or honoraria from Boehringer Ingelheim for his role as a consultant\/advisory board member as well as from Skye Bioscience, Zealand Pharmaceuticals, Jamieson Wellness and Pfizer for lectures. He has received support for attending meetings and\/or travel from Jamieson Wellness for his role as a consultant\/advisory board member. He has patents pending with FlyteHealth and has served on the board of directors for FlyteHealth, Jamieson Wellness and ERX Pharmaceuticals. He holds equity interests in Jamieson Wellness, FlyteHealth, Kallyope, Mediflix, Metsera, MBX Bioscience, Syntis, Veru Pharmaceuticals and Skye Bioscience. P.M. has nothing to disclose. L.B.K. is a former employee and shareholder of Versanis Bio and a former employee of Lilly. He is an inventor or co-inventor on the following patents assigned to Versanis Bio: US20240368291A1 (ActRII antibody treatments), WO2024044782A1 (ActRII antibody fixed-dose treatments) and US20240325530A1 (combination therapies). L.A.C. is an employee and shareholder of Lilly. She is a former employee of Versanis Bio with equity holdings. She also has a pending patent (PAT058683-US-PSP). K.D. is an employee and shareholder of Lilly. She is also a former employee of Versanis Bio with equity holdings. L.M. is a former consultant to Versanis Bio with equity holdings. She is now a consultant to Lilly. S.S. was a former consultant to Versanis Bio and is now a consultant to Lilly. X.L. is an employee and stockholder of Lilly. K.M.A. is an employee and shareholder of Lilly. He is also a former employee of Versanis Bio with equity holdings.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}