Survodutide (BI 456906) is a next-generation dual glucagon receptor (GCGR) and GLP-1 receptor agonist developed by Boehringer Ingelheim.
Structure & Design
Survodutide is derived from native glucagon with modifications including a C18 fatty diacid for once-weekly dosing. It provides balanced dual agonism at both GCGR and GLP-1R.
Dual Mechanism
GLP-1 Receptor Activation
- Glucose-dependent insulin secretion
- Appetite suppression
- Delayed gastric emptying
Glucagon Receptor Activation
- Increased energy expenditure
- Enhanced lipid oxidation
- Hepatic fat reduction
- Thermogenesis stimulation
Clinical Trial Results
Obesity Phase 2 (2024)
- 4.8mg dose: -14.9% weight loss vs -2.8% placebo
MASH Phase 2 (NEJM 2024)
- MASH improvement: 62% (4.8mg) vs 14% placebo
- ≥30% liver fat reduction: 67% vs 14% placebo
Regulatory Status
- FDA Breakthrough Therapy designation for noncirrhotic MASH
- Phase 3 trials initiated October 2024:
- LIVERAGE: ~1,800 adults with MASH fibrosis stages 2-3
- LIVERAGE-Cirrhosis: ~1,590 adults with compensated cirrhosis
- SYNCHRONIZE-CVOT: Cardiovascular outcomes
Safety
Adverse events primarily gastrointestinal (nausea, vomiting, diarrhea). All tested doses tolerated.