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

In a phase 3 trial, 48 weeks of survodutide 6.0 mg once weekly produced significantly greater reductions in liver fat and body weight than placebo in 216 adults with obesity and at-risk MASLD. 84.2% of survodutide-treated versus 24.3% of placebo-treated participants achieved at least a 30% reduction in liver fat, and mean body weight fell by 12.2% versus 1.0%. Gastrointestinal adverse events were common but mostly mild to moderate.

Late-phase clinical trial — randomized double-blind placebo-controlled phase 3 trial. Population: adults with obesity and at-risk metabolic dysfunction-associated steatotic liver disease (MASLD). Sample size: 216 adults. Follow-up: 48 weeks. Interventions: Survodutide 6.0 mg once-weekly subcutaneous injection.

The co-primary endpoints were met. Using the efficacy estimand, 84.2% of survodutide-treated patients versus 24.3% of placebo-treated patients achieved ≥30% reduction in liver fat content (P < 0.0001); the treatment regimen estimand showed 68.5% versus 28.6% (P < 0.0001). Mean percentage change in body weight was -12.2% with survodutide versus -1.0% with placebo using the efficacy estimand (P < 0.0001) and -8.7% versus -1.4% with the treatment regimen estimand (P < 0.0001). The most frequently reported adverse events with survodutide were gastrointestinal, generally of mild-to-moderate severity and occurring during dose escalation.

For researchers working on Survodutide, this paper provides robust phase 3 evidence that the dual agonist reduces liver fat and body weight in adults with obesity and at-risk MASLD over 48 weeks. It does not establish histologic reversal of MASH, cardiovascular outcomes, or durability of weight loss beyond 48 weeks, and comparisons to other agents are absent.

Key findings

• 84.2% of survodutide-treated versus 24.3% of placebo-treated patients had ≥30% reduction in MRI-PDFF-assessed liver fat content (efficacy estimand, P < 0.0001).
• Treatment regimen estimand showed 68.5% versus 28.6% achieving ≥30% liver fat reduction (P < 0.0001).
• Mean percentage change in body weight was -12.2% with survodutide versus -1.0% with placebo (efficacy estimand, P < 0.0001).
• Treatment regimen estimand for body weight change was -8.7% versus -1.4% (P < 0.0001).
• The co-primary endpoints were met at week 48.

Limitations

• Short trial duration (48 weeks)
• Limited global reach (participants recruited only in the United States and Spain)
• No histologic or longer-term outcome data reported
• No active comparator, only placebo

The record

• Journal: Nature medicine 32(8): 2948-2958
• Published: 2026-06-07
• PMID: 42252333 — DOI: 10.1038/s41591-026-04479-3
• MeSH terms: Liver, Humans, Fatty Liver, Obesity, Magnetic Resonance Imaging, Body Mass Index, Double-Blind Method, Adult, Middle Aged, Female, Male
• Author countries: Canada, Germany, Ireland, UK, USA

Peptide profiles: Survodutide.

All indexed evidence: Survodutide trials & papers.

Related studies: Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell…, Survodutide Once Weekly for the Treatment of Adults with Obesity, Author Correction: Survodutide in adults with obesity and metabolic…, Survodutide for Obesity in Chinese Adults: Phase 3 Randomized Trial Design and Baseline….