Survodutide
From PeptidePlaza, the free peptide reference · Entry #033 · Metabolic · Hand-curated entry · Editorial standards
Survodutide (also known as BI 456906, BI-456906, NNC9204-4276) is a metabolic research peptide. A 29-amino-acid dual agonist that pairs GLP-1 appetite suppression with glucagon-driven energy expenditure and hepatic fat oxidation. Its liver-fat data is the standout: up to 63% reduction.
Survodutide is an acylated 29-amino-acid peptide developed by Boehringer Ingelheim and Zealand Pharma that co-activates the glucagon receptor (GCGR) and the GLP-1 receptor. The design logic differs from GIP/GLP-1 co-agonism: glucagon receptor activation increases resting energy expenditure and drives hepatic lipolysis and fatty acid oxidation, while GLP-1 agonism suppresses appetite and offsets glucagon's hyperglycaemic effect. In the phase 3 SYNCHRONIZE-1 trial, adults with obesity or overweight without type 2 diabetes achieved up to 16.6% mean weight loss at 76 weeks versus 3.2% with placebo, with up to 85.1% achieving ≥5% weight loss. Body-composition data showed visceral fat reduction of up to 34% and liver fat reduction of up to 63.1%, with lean mass accounting for no more than 10.8% of total tissue change at the highest dose. A phase 2 trial in MASH (NEJM, 2024) showed superiority over placebo for histological improvement in steatohepatitis without worsening fibrosis. Gastrointestinal tolerability is the principal limitation — 19.0% of survodutide participants discontinued for GI adverse events versus 2.9% on placebo.
1 Mechanism of action
Co-activates GCGR and GLP-1R. Glucagon receptor agonism raises resting energy expenditure and stimulates hepatic fatty acid oxidation and lipolysis; GLP-1 receptor agonism suppresses appetite, slows gastric emptying and counterbalances glucagon-induced hepatic glucose output.
Primary targets: GCGR · GLP-1R
2 Reported effects
Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.
2.1 Reported benefits
- Up to 16.6% mean weight loss at 76 weeks in phase 3 (SYNCHRONIZE-1)
- Up to 63.1% reduction in liver fat content
- Up to 34% reduction in visceral adipose tissue
- Histological improvement in MASH without fibrosis worsening (phase 2)
- Increases resting energy expenditure via glucagon receptor agonism
- Lean mass preserved as ≥89% of tissue retained at the highest dose
2.2 Side effects
- Gastrointestinal events driving 19.0% discontinuation in phase 3
- Nausea, vomiting, diarrhoea, constipation (dose- and escalation-rate dependent)
- Increased heart rate (class effect of glucagon/GLP-1 agonists)
- Injection site reactions
- Transient rise in hepatic enzymes in some participants
- Appetite suppression sufficient to compromise nutrient intake
3 Chemical and physical properties
| CAS number | 2805997-46-8 |
|---|---|
| Molar mass | 4231.69 g/mol |
| Purity (typical) | >98% |
| Half-life | ~6 days (SC injection; weekly dosing) |
| Storage | −20 °C, lyophilised powder, desiccated |
| Solubility | Sterile water / bacteriostatic water |
| Receptors / targets | GCGR, GLP-1R |
3.1 Amino acid sequence
Acylated 29-residue glucagon/GLP-1 co-agonist peptide bearing a C18 fatty acid side chain via a γGlu spacer
4 Research dosages
Phase 2/3 protocols escalated to 3.6 mg or 6.0 mg SC once weekly over 16–24 weeks; slower escalation materially improved GI tolerability.
5 Research studies (7)
- A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis
New England Journal of Medicine (2024) · RCT · N=29348-week phase 2 trial in biopsy-confirmed MASH with F1–F3 fibrosis.Key finding: Survodutide was superior to placebo for histological improvement in MASH without worsening of fibrosis, supporting progression to phase 3. - Beyond weight loss: multisystem benefits of obesity medications.
The lancet. Diabetes & endocrinology (2026) · ReviewObesity is increasingly managed with medications as disease-modifying therapies, reflecting its role as a gateway disease driving metabolic, cardiovascular, reproductive, neuropsychiatric, and mechanical... - Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA.
Obesity (Silver Spring, Md.) (2025) · Systematic ReviewRetatrutide offers superior weight loss efficacy but with a higher AE risk. - Emerging pharmacotherapies for obesity: A systematic review.
Pharmacological reviews (2025) · Systematic ReviewThe history of antiobesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the prevailing conviction that excess body weight signifies a lack of... - Weight management treatment in obesity.
Medicina clinica (2025) · ReviewObesity is a chronic and relapsing disease associated with medical complications and mortality. - A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.
The New England journal of medicine (2024) · RCTSurvodutide was superior to placebo with respect to improvement in MASH without worsening of fibrosis, warranting further investigation in phase 3 trials. - Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity.
Diabetes care (2024) · ReviewThe development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits of GLP-1RA in select patient populations.
6 Safety and risk profile
6.1 Regulatory status
Survodutide is currently classified as Phase 3 clinical trials. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.
Safety score: 65/100 — moderate concern. Derived from clinical data volume, known risks and regulatory status.
6.2 Contraindications
Conditions and populations in which use is contraindicated:
- Personal or family history of medullary thyroid carcinoma or MEN2 (class precaution)
- History of pancreatitis
- Severe gastroparesis
- Pregnancy or lactation
- Type 1 diabetes mellitus
6.3 Drug interactions
| Drug or class | Interaction | Risk |
|---|---|---|
| Insulin / sulfonylureas | Complex — GLP-1 component increases hypoglycaemia risk, glucagon component opposes it; unpredictable net effect requires close glucose monitoring. | High |
| Oral drugs with narrow therapeutic index | Delayed gastric emptying alters absorption kinetics. | Moderate |
| Beta blockers | May mask the tachycardia associated with glucagon receptor agonism. | Low |
6.4 Long-term risks
- No data beyond the 76-week phase 3 horizon
- Sustained increase in heart rate of uncertain long-term consequence
- Unknown effects of chronic glucagon receptor agonism on hepatic amino acid metabolism
- Weight regain on discontinuation
6.5 Research best practices
- Store lyophilised at −20 °C; reconstituted at 2–8 °C
- Extend escalation intervals to 4 weeks minimum — GI discontinuation is the dominant failure mode
- Monitor heart rate, hepatic enzymes and glycaemia in extended protocols
- Maintain protein intake to protect lean mass during rapid loss
7 Frequently asked questions
- How is survodutide different from tirzepatide?
- Tirzepatide co-activates GIP and GLP-1 receptors; survodutide co-activates glucagon and GLP-1 receptors. Glucagon receptor agonism adds an energy-expenditure and hepatic fat-oxidation component that GIP agonism does not provide, which is why survodutide's liver fat reduction data (up to 63%) is so pronounced.
- Doesn't glucagon raise blood sugar?
- On its own, yes. The GLP-1 component of the molecule opposes that effect by stimulating glucose-dependent insulin secretion and suppressing endogenous glucagon signalling downstream, so net glycaemic effect in trials has been favourable. This balance is why the GLP-1:glucagon potency ratio is a critical design parameter.
- What is the main tolerability problem?
- Gastrointestinal adverse events. In SYNCHRONIZE-1, 19.0% of participants on survodutide discontinued because of GI events versus 2.9% on placebo — a notably higher discontinuation rate than seen with GLP-1 monotherapy.
8 References
- Beyond weight loss: multisystem benefits of obesity medications. PubMed (2026). Savas M, et al.. View source
- Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA. PubMed (2025). Sinha B, et al.. View source
- Emerging pharmacotherapies for obesity: A systematic review. PubMed (2025). Kokkorakis M, et al.. View source
- Weight management treatment in obesity. PubMed (2025). Rubio-Herrera MA, et al.. View source
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