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The SYNCHRONIZE-MASLD phase 3, randomized, double-blind, placebo-controlled trial included 216 adults (131 female and 85 male) with obesity (defined as a 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 complication) and at-risk metabolic dysfunction-associated steatotic liver disease (MASLD), defined by MASLD with evidence of liver inflammation and\/or fibrosis by noninvasive tests (NITs) or biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH). Participants were randomized (2:1) and treated with once-weekly subcutaneous injections of survodutide 6.0\u2009mg (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009146) or placebo (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200970). The co-primary endpoints, \u226530% reduction in magnetic resonance imaging-proton density fat fraction (MRI-PDFF)-assessed liver fat content (LFC) and percentage change in body weight (both baseline to week 48), were met. In total, 84.2% of survodutide-treated patients versus 24.3% of placebo-treated patients had \u226530% reduction in LFC using the efficacy estimand (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001; treatment regimen estimand: 68.5% versus 28.6%, respectively;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Mean percentage change in body weight was \u221212.2% with survodutide and \u22121.0% with placebo using the efficacy estimand (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001; treatment regimen estimand: \u22128.7% versus \u22121.4%, respectively;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001). The most frequently reported adverse events with survodutide were gastrointestinal, commonly occurring during dose escalation, and were generally of mild-to-moderate severity. In adults with obesity and at-risk MASLD, survodutide treatment was statistically and clinically superior to placebo for reductions in MRI-PDFF-assessed LFC and body weight. Limitations included short trial duration (48\u2009weeks) and limited global reach (participants recruited in the United States and Spain).\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04479-3","type":"journal-article","created":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T19:01:36Z","timestamp":1780858896000},"page":"2948-2958","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6301-2696","authenticated-orcid":false,"given":"Lee 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Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Survodutide is licensed to Boehringer Ingelheim from Zealand Pharma, with Boehringer solely responsible for development and commercialization globally. L.M.K. has served as a scientific and medical consultant to Altimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Dexligo, Dil Figaro, Eli Lilly, Helicore, Johnson & Johnson, Kallyope, The Last Food Fight, MetaVia, Neurogastrx, Novo Nordisk, Optum Health, Oxford Medical Products, Perspectum, Pfizer, Roche\/Genentech, Skye Bioscience, State 4 Therapeutics, Structure Therapeutics and Wave Life Sciences. C.l.R. has received personal fees from Boehringer Ingelheim, Eli Lilly, GI Dynamics, Herbalife, Johnson & Johnson, Keyron and Novo Nordisk, outside the submitted work. S.W. has conducted multicenter trials with Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer and Roche; serves on scientific advisory boards for AbbVie, Amgen, AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly, i2o Therapeutics, Merck, Metsera, NGX, Novo Nordisk and Regeneron; and receives institutional grant funding from the Canadian Institutes of Health Research. B.B. has served as a consultant or advisor for ABIOMED\/Johnson & Johnson, Bayer, Boehringer Ingelheim, Cardurion, Cytokinetics, Eli Lilly, Idorsia, Medtronic, Merck, Novo Nordisk, Regeneron, Renovacor, Roche, Salubris, Sanofi-Aventis, scPharmaceuticals, Respicardia\/Zoll and Vifor. G.W.N. received research grant support from Akero, Allergan, Altimmune, Bristol Myers Squibb, Boehringer Ingelheim, Boston Pharma, Corcept, Genfit, Gilead, GlaxoSmithKline, Eli Lilly, Madrigal, Merck, Novartis, Novo Nordisk and Takeda and consulted for Boehringer Ingelheim and Intercept Pharmaceuticals. A.J.S. has stock options for Durect, NorthSea, Rivus and Tiziana; has consulted for 89Bio, AbbVie, Akero, Aligos, Alnylam, Altimmune, Amgen, AstraZeneca, Avant Sante, Boehringer Ingelheim, Boston Pharma, Chemomab, Corcept, Eli Lilly, Genentech, Genfit, GlaxoSmithKline, Hanmi, Histoindex, Intercept, Inventiva, Madrigal, Malinckrodt, Medscape, Merck, Myovant, Novo Nordisk, Pliant, Poxel, Regeneron, Sagimet, Salix, Surrozen and Takeda; has received research grants to the institution from 89Bio, Gilead, Hanmi, Intercept, Madrigal, Merck, Novo Nordisk and Salix; and receives royalties from Elsevier and UpToDate. E.S., D.F.M., J.v.S., S.G.M., S.A.H. and R.Y. are employees of Boehringer Ingelheim. The remaining authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}