Scientific Reference
Survodutide (BI 456906)
Evidence profile: Human Phase 3 evidence
Survodutide (BI 456906) is an investigational dual glucagon receptor (GCGR) and GLP-1 receptor (GLP-1R) agonist designed for once-weekly subcutaneous administration. This 29-amino acid peptide with C18 fatty acid acylation represents a novel approach to metabolic disease treatment by simultaneously targeting both energy intake reduction (via GLP-1R) and energy expenditure increase (via GCGR). The compound has demonstrated robust efficacy in clinical trials for obesity and metabolic dysfunction-associated steatohepatitis (MASH), showing superior weight loss versus semaglutide in head-to-head comparisons. Its dual mechanism addresses both energy intake and expenditure, potentially reducing weight regain compared to single-receptor approaches.
Mechanism of Action
Survodutide acts as a dual agonist at glucagon receptors and GLP-1 receptors. GLP-1 receptor activation suppresses appetite, slows gastric emptying, and improves glycemic control, while glucagon receptor activation increases energy expenditure and promotes hepatic fat oxidation. This balanced dual agonism produces additive metabolic effects, enabling significant weight reduction and improved metabolic health.
Molecular Information
- Type: Dual GCGR/GLP-1R agonist (acylated peptide)
- Length: 29 amino acids
- Molecular weight: 4232 g/mol
- Molecular formula: C192H289N47O61
Published Research
SYNCHRONIZE-1
Survodutide Once Weekly for the Treatment of Adults with Obesity
le Roux CW et al. · The New England journal of medicine · 2026 · Clinical
PMID 42253238 — View on PubMedSYNCHRONIZE-MASLD
Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial
Kaplan LM et al. · Nature medicine · 2026 · Clinical
PMID 42252333 — View on PubMedA Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis
Sanyal AJ et al. · The New England journal of medicine · 2024 · Clinical
PMID 38847460 — View on PubMedGlucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial
le Roux CW et al. · The lancet. Diabetes & endocrinology · 2024 · Clinical
PMID 38330987 — View on PubMedBaseline characteristics in the SYNCHRONIZE™-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes
Wharton S et al. · Diabetes, obesity & metabolism · 2026 · Clinical
PMID 41216778 — View on PubMedDose-response effects on HbA(1c) and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial
Blüher M et al. · Diabetologia · 2024 · Clinical
PMID 38095657 — View on PubMed