Survodutide (BI-456906) — Dual GLP-1/Glucagon Receptor Agonist

What it is
Survodutide is a long-acting peptide that co-activates the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It’s engineered from the native glucagon backbone and lipid-modified for once-weekly dosing. Intended for advanced research use, it sits at the intersection of energy-balance biology, liver metabolism, and appetite regulation. ScienceDirect+1

How it works (mechanism & pathways)

• GLP-1R agonism slows gastric emptying, enhances glucose-dependent insulin secretion, and reduces appetite via central and peripheral signaling.

• GCGR agonism increases energy expenditure and promotes hepatic lipid mobilization/oxidation.
  The combination drives negative energy balance through lower caloric intake and higher energy expenditure, a profile repeatedly demonstrated in preclinical models and early human studies. PubMed Central

Why dual agonism matters
Unlike pure GLP-1 agonists, the added glucagon tone appears to amplify weight-loss biology and may directly benefit liver fat and fibrosis pathways relevant to MASH (metabolic dysfunction–associated steatohepatitis). ScienceDirect

Key clinical findings (Phase 2)

• Obesity/overweight (no diabetes): Randomized dose-finding data show meaningful, dose-dependent weight loss over 46 weeks; multiple reports cite ~12–15%+ mean loss at higher doses, with more than half of participants on 4.8 mg achieving ≥15% loss. GI events (nausea, vomiting) were the most common and resembled GLP-1RA class effects. pace-cme.org+1

• MASH with fibrosis: In a pivotal Phase 2 trial (NEJM), survodutide significantly improved MASH without worsening fibrosis vs. placebo, with dose-response across 2.4–6.0 mg. Company releases highlight substantial fibrosis improvement rates and subsequent Breakthrough Therapy designation and Phase 3 initiation. Boehringer Ingelheim+3New England Journal of Medicine+3PubMed+3

What researchers observe

• Body-weight effects: Lower energy intake + higher expenditure leading to robust weight reductions across doses and time. PubMed Central

• Liver & metabolic signals: Histologic and non-invasive improvements in MASH endpoints and fibrosis measures in mid-stage trials. New England Journal of Medicine+1

• Tolerability: Class-typical GLP-1–like GI profile; safety continues to be characterized in ongoing Phase 3 programs. pace-cme.org+1

Bio Peptide Technologies — Research-ready specs

• Identity: Survodutide (BI-456906)

• CAS: 2805997-46-8

• Formula / MW: C₁₉₂H₂₈₉N₄₇O₆₁; ~4,231.6 g/mol

• Design: Glucagon-derived sequence with C18 fatty diacid acylation enabling once-weekly PK behavior (albumin binding & extended half-life). PubChem+2MedChemExpress+2

Intended use
For laboratory research only. Not for human consumption, clinical use, compounding, or veterinary applications.