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

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).