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Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass. In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009102) were randomized 1:1 to receive tirzepatide plus apitegromab (10\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) or tirzepatide plus placebo. At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2\u22122.7) kg less lean mass loss than placebo (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo. In participants receiving apitegromab, trough concentrations of apitegromab and total latent myostatin, a pharmacodynamic marker, both increased over time and reached a plateau after approximately 16\u2009weeks. Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63\u221286%)) and 36 of 51 (71% (57\u221281%)) participants experiencing an AE, respectively. Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0\u221210%)) participants in each arm. In summary, this proof-of-concept study demonstrated that selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. ClinicalTrials.gov identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/study\/NCT06445075\" ext-link-type=\"uri\">NCT06445075<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04440-4","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:03:13Z","timestamp":1780930993000},"page":"2673-2678","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-1389","authenticated-orcid":false,"given":"Richard E.","family":"Pratley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas Scott","family":"Denham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupal","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Connery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongzi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Simard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2717-8265","authenticated-orcid":false,"given":"Kimberly","family":"Umans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giridhar S.","family":"Tirucherai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing L.","family":"Marantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"4440_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1056\/NEJMoa1614362","volume":"377","author":"A Afshin","year":"2017","unstructured":"Afshin, A. et al. 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D.S.D. reports no conflicts related to this work. R.T. reports no conflicts related to this work. E.W. reports no conflicts related to this work. L.C. has served on advisory boards for Boehringer Ingelheim, Lilly and Intarcia and has received research funding from Amgen, Argo, AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Novo Nordisk, Pfizer, Regeneron, Regor, Roche, Scholar Rock, Structure\/Gasherbrum, Vanda, Verdiva, Viking and Zealand. D.Y., J.H., C.S., K.U., L.L., G.S.T. and J.L.M. are employees of Scholar Rock, Inc. and may hold stock\/stock options in the company. J.B. was affiliated with Scholar Rock at the time the study was conducted.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}