Logo image
Back
Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial
Journal article   Open access   Peer reviewed

Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial

Lee M Kaplan, Elena Startseva, Carel W. le Roux, Sean Wharton, Biykem Bozkurt, Daniel F. Mazo, Jessica von Schlippenbach, Sandra González Maldonado, Samina Ajaz Hussain, Guy W Neff, …
Nature medicine, Vol.32(8), pp.2948-2958
08/2026
DOI: 10.1038/s41591-026-04479-3
PMCID: PMC13472939
PMID: 42252333
url
https://doi.org/10.1038/s41591-026-04479-3View
Published (Version of record) Open Access

Related content

Was corrected by

Abstract

Survodutide is a glucagon receptor/glucagon-like peptide-1 receptor dual agonist under investigation for treating obesity and related diseases. 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 ≥30 kg m−2 or ≥27 kg m−2 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 mg (n = 146) or placebo (n = 70). The co-primary endpoints, ≥30% 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 ≥30% reduction in LFC using the efficacy estimand (P < 0.0001; treatment regimen estimand: 68.5% versus 28.6%, respectively; P < 0.0001). Mean percentage change in body weight was −12.2% with survodutide and −1.0% with placebo using the efficacy estimand (P < 0.0001; treatment regimen estimand: −8.7% versus −1.4%, respectively; P < 0.0001). 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 weeks) and limited global reach (participants recruited in the United States and Spain).

Details

Metrics

1 Record Views
7 Times Cited - Web of Science
Logo image