Survodutide
Survodutide (BI 456906)
Investigational once-weekly dual GLP-1 / glucagon receptor agonist. SYNCHRONIZE-1 phase 3 readout (Apr 28, 2026): 16.6% mean weight loss at 76 weeks in obesity without T2D. Efficacy positioned between high-dose semaglutide and tirzepatide, but with the glucagon agonism advantage in MASH (phase 2 NEJM 2024 showed 47-62% MASH improvement). FDA Breakthrough Therapy designation for MASH (2024). Targets the MASH market plus mainstream obesity.
At a glance
- Half-life
- ~6 days ~6 days. Linear PK. Albumin binding >99%. Confirmed across healthy and cirrhosis populations.
- Routes
- SubQ
- Evidence base
- 4 studies 4 human
Mechanism
Dual receptor agonist at GLP-1R and glucagon receptor (GCGR). Engineered for balanced activity with strong albumin binding (>99%; t½ ~6 days, confirmed across cirrhosis severity) for once-weekly dosing. GLP-1R drives standard incretin effects (insulin secretion, gastric emptying, hypothalamic appetite). GCGR increases hepatic lipid oxidation, energy expenditure, ketogenesis: the MASH-targeting component. Phase 2 obesity: -14.9% at 4.8mg vs -2.8% placebo; MASH phase 2: 47-62% MASH improvement; SYNCHRONIZE-1 phase 3: -16.6% vs -3.2% placebo.
Dosing
Any amounts shown here are reported from published studies only. 4 of 4 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.
Where a study reports an amount, it appears in that study's entry below, attributed to the source.
Published evidence
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Human RCT 2026
SYNCHRONIZE-1 topline phase 3 results
Phase 3 obesity n=~700, 76 weeks: survodutide -16.6% body weight vs placebo -3.2%. 85.1% achieved ≥5% loss. Met both co-primary endpoints. Full data ADA June 2026.
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Human RCT 2024
Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial
Phase 2 obesity, n=387, 46 weeks: 0.6mg -6.2%, 2.4mg -12.5%, 3.6mg -13.2%, 4.8mg -14.9% vs placebo -2.8%. GI AEs 75% vs 42% placebo.
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Human RCT 2024
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis
MASH phase 2, n=293, 48 weeks. MASH improvement w/o fibrosis worsening: 47% (2.4mg), 62% (4.8mg), 43% (6mg) vs 14% placebo. Hepatic fat reduction ≥30%: 57-67% vs 14% placebo. Fibrosis improvement ≥1 stage: 34-36% vs 22% placebo. Basis for FDA Breakthrough Therapy.
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Human RCT 2024
Survodutide PK in cirrhosis
Survodutide PK in healthy + cirrhosis: t½ ~6 days, albumin binding >99%, linear PK across cirrhosis severity.
Reported side effects
- Nausea
- Very common Moderate · Phase 2 obesity: 75% of survodutide pts had GI AEs vs 42% placebo. Most common AE.
- Vomiting
- Common Moderate · Phase 2: 30-40% across higher-dose arms.
- Diarrhea
- Common Mild · Phase 2: 25-35%.
- Constipation
- Common Mild · Phase 2: 15-22%.
- Decreased appetite
- Very common Mild · Wanted effect; reported as AE in 20-30%.
- Heart rate increase
- Common Mild · Mean +3-7 bpm at higher doses (glucagon-driven).
- Hepatic enzyme changes
- Occasional Mild · MASH phase 2: hepatic fat reduction 57-67%; ALT improvements concomitant. Few discontinuations for hepatic AEs.
- Injection site reactions
- Common Mild · Standard SC peptide profile.
- Pancreatitis
- Rare Serious · Class warning expected. No elevated rates reported in phase 2/3 to date.
- Thyroid C-cell tumors
- Rare Serious · Class warning expected at approval.
Interactions
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Insulin or sulfonylurea Synergy
Hypoglycemia risk with insulin or SU. GLP-1 component drives glucose-dependent insulin secretion; glucagon component partially counters but net effect is glucose lowering.
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Oral medications (general) Absorption interference
GLP-1 mediated gastric emptying delay may affect absorption of oral drugs.
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Semaglutide (SC) Redundant
Overlapping GLP-1 agonism. Concurrent GLP-1 RA not recommended.
Reconstitution and storage
N/A pre-approval.
N/A pre-approval.