Survodutide: Mechanism, Research & UK Safety Profile
Also known as: BI 456906
Investigational once-weekly GLP-1 / glucagon dual receptor agonist co-developed by Boehringer Ingelheim and Zealand Pharma. Phase 3 programmes in obesity (BI-Obesity-1) and MASH (FDA Breakthrough Therapy designation). Not licensed for human therapeutic use in the UK at the time of review.
Molecular formula
C192H289N47O61
Molecular weight
Approx. 4.2 kDa (~4,232 g/mol)
Half-life
Engineered for once-weekly dosing via albumin binding.
Category
GLP-1 / glucagon dual agonist
Overview
Survodutide (BI 456906) is an investigational long-acting peptide that activates both the GLP-1 receptor and the glucagon receptor. The integrated rationale is that combining incretin-driven appetite suppression with glucagon-driven energy expenditure and hepatic fat oxidation produces a metabolic effect distinct from GLP-1 mono-agonism. Phase 2 obesity data reported double-digit mean body-weight reductions and the programme has progressed into phase 3 for obesity and MASH, the latter with US FDA Breakthrough Therapy designation. Survodutide is not licensed for human therapeutic use anywhere at the time of review.
Discovery & Research History
Survodutide emerged from the Boehringer Ingelheim / Zealand Pharma collaboration. Phase 1 and phase 2 studies (NEJM 2024, Lancet 2024) characterised the obesity and MASH signal. The phase 3 obesity programme (multiple BI-Obesity studies) and the phase 3 MASH programme are in active enrolment / readout cycle.
Mechanism of Action
Dual agonism of GLP-1 and glucagon receptors. GLP-1 agonism drives glucose-dependent insulin secretion, central appetite suppression and gastric-emptying delay; glucagon receptor agonism increases energy expenditure and hepatic fat oxidation. The fixed ratio of GLP-1 to glucagon activity is engineered to preserve glycaemic safety while delivering the metabolic benefit of glucagon activation.
Researched Effects
- Body-weight reduction in adults with overweight or obesity in phase 2 trials.
- Reduction in hepatic fat by MRI-PDFF and improvement in liver-injury markers in MASH-focused phase 2 data.
- FDA Breakthrough Therapy designation for MASH (2024).
Theoretical Research Protocols
- Dosage range
- Trial-arm doses are research records. This page is not a prescribing or self-administration guide.
- Frequency
- Once-weekly subcutaneous administration in trial protocols.
- Duration
- 46-72 weeks in phase 2 / phase 3 obesity and MASH designs.
- Administration routes
- Subcutaneous (clinical trial setting)
Safety Profile
Common side effects (research)
- Gastrointestinal events (nausea, vomiting, diarrhoea, constipation) consistent with the GLP-1 / glucagon class profile.
- Injection-site reactions.
Rare risks
- Heart-rate increase has been reported with glucagon-receptor-containing combinations and is a class-monitored signal.
- Long-term cardiovascular, hepatic, retinal and pancreatic safety remains to be characterised through dedicated outcome trials.
Contraindications
- Investigational compound — eligibility is defined by the relevant clinical trial protocol.
- Pregnancy and breastfeeding are typical trial exclusions.
UK Regulatory Status
United Kingdom (MHRA): Investigational. Not MHRA-licensed for any human therapeutic indication.
European Union (EMA): Investigational.
Notes: Survodutide is investigational across all major jurisdictions at the time of review. Use is restricted to authorised, ethically approved clinical research.
Related research resources
Key Research Studies
le Roux CW et al. Survodutide for treatment of obesity — phase 2. NEJM 2024.
Phase 2 trial in adults with obesity reporting substantial mean percent body-weight reduction with survodutide versus placebo across multiple dose arms.
Read sourceSanyal AJ et al. Survodutide for MASH — phase 2. NEJM 2024.
Phase 2 trial in adults with biopsy-confirmed MASH reporting histological improvement with survodutide versus placebo. Supported FDA Breakthrough Therapy designation.
Read sourceBoehringer Ingelheim phase 3 obesity programme (BI-Obesity-1, BI-Obesity-2)
Phase 3 evaluation of survodutide for obesity. Topline readout cycle ongoing during 2024-2026; refer to current ClinicalTrials.gov records and the primary publications for results.
Frequently Asked Questions
What is survodutide?
An investigational long-acting GLP-1 / glucagon dual receptor agonist co-developed by Boehringer Ingelheim and Zealand Pharma. Phase 3 programmes for obesity and MASH are in active enrolment / readout.
Is survodutide licensed in the UK?
No. Survodutide is investigational and is not licensed by the MHRA for any human therapeutic indication.
How does survodutide differ from tirzepatide?
Tirzepatide is a GLP-1 / GIP dual agonist; survodutide is a GLP-1 / glucagon dual agonist. The added glucagon-receptor component is hypothesised to drive energy expenditure and hepatic fat oxidation. Head-to-head trials have not been published at the time of review.
Related trials
No published trials yet linked to this page. Source verification required.