Survodutide for the treatment of obesity: Mechanistic rationale, clinical evidence, and remaining uncertainties.

Survodutide (BI 456906) is an investigational once-weekly dual glucagon and Glucagon-like Peptide (GLP-1) receptor agonist being developed for obesity. In a phase 2 trial involving adults with a body mass index ≥27 kg/m2 without diabetes, participants assigned to the 4.8-mg dose achieved a mean body-weight reduction of up to 18.7% at 46 weeks, compared with 2.3% with placebo. Its proposed mechanism combines reduced food intake through GLP-1 receptor agonism with glucagon receptor-mediated effects on energy expenditure and hepatic metabolism. Gastrointestinal adverse events, including nausea, vomiting, and diarrhea, were common and were influenced by dose escalation. Phase 3 SYNCHRONIZE trials are evaluating efficacy, safety, and tolerability in broader populations with and without type 2 diabetes. Survodutide is not approved for routine clinical use, and its comparative effectiveness, durability, long-term safety, treatment persistence, and effects after discontinuation remain to be established.