Survodutide in obesity and MASLD: Results from a phase 3 trial

Kaplan LM et al, Nat Med. 2026 [ahead of print]
In a randomized, double-blind, placebo-controlled phase 3 trial, survodutide, a dual glucagon/GLP-1 receptor agonist, was evaluated in adults with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Survodutide resulted in significant weight loss and marked improvements in steatohepatitis as well as non-invasive markers of liver fibrosis compared with placebo. These findings highlight the potential of survodutide as a promising therapeutic option for patients with MASLD.

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/m2 or ≥ 27 kg/m2 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