Survodutide
/ Dual GLP-1 / glucagon receptor agonist (Boehringer Ingelheim + Zealand Pharma)ALIAS · BI-456906 · Survodutide
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Tier 2. Phase 2 obesity data published (le Roux and colleagues, Lancet Diabetes Endocrinol 2024). The SYNCHRONIZE Phase 3 obesity program and SCYNERGISE Phase 3 metabolic dysfunction-associated steatohepatitis (MASH) program are ongoing. Boehringer Ingelheim and Zealand Pharma co-development; not approved.
Survodutide is a synthetic dual agonist of the GLP-1 receptor and the glucagon receptor, lipid-acylated for albumin binding to support once-weekly subcutaneous dosing. The dual pharmacology — GLP-1 receptor agonism plus glucagon receptor agonism — is intended to combine the established weight-loss and glycaemic effects of GLP-1 monotherapy with additional energy expenditure and hepatic effects from glucagon receptor activation. Glucagon receptor agonism is hypothesised to be particularly relevant for hepatic steatosis: glucagon stimulates hepatic fatty acid oxidation and reduces hepatic de novo lipogenesis, providing a mechanistic basis for the MASH indication.
Tier 2. The Phase 2 obesity trial (le Roux and colleagues, Lancet Diabetes & Endocrinology 2024) randomised 387 adults with obesity to survodutide or placebo and reported dose-dependent weight reduction (up to 18.7% mean change at 46 weeks at the highest dose). Phase 2 MASH data have been reported. The SYNCHRONIZE Phase 3 obesity program and the SCYNERGISE Phase 3 MASH program are ongoing.
Phase 2 common adverse events included nausea, vomiting, diarrhoea, and decreased appetite, consistent with class effects of GLP-1 receptor agonism; gastrointestinal AEs were dose-related. Glucagon receptor agonism raises specific safety questions about hepatic glucose output and lipid effects; the published Phase 2 data have not flagged unexpected hepatic safety signals at the doses studied. Pancreatitis and class C-cell tumour concerns apply.
Regulatory status
- FDA status:
- Not FDA-approved
The dual GLP-1/glucagon receptor agonist class includes survodutide, mazdutide, and the discontinued cotadutide (AstraZeneca). Whether the additional glucagon receptor agonism translates to clinically meaningful efficacy benefit (in obesity, MASH, or both) at acceptable safety is the open Phase 3 question. The MASH indication, if positive, would be the first GLP-1-class approval for a hepatic-fibrosis endpoint. Vendor research-grade 'survodutide' is not interchangeable with clinical-grade material.