Survodutide
BI 456906
Survodutide (BI 456906) is a GLP-1/glucagon receptor dual agonist developed by Boehringer Ingelheim in partnership with Zealand Pharma. It activates GLP-1 receptors for appetite suppression and glycemic control while engaging glucagon receptors to promote hepatic fat oxidation and increased energy expenditure. It is in Phase 3 clinical trials for both obesity and metabolic dysfunction-associated steatohepatitis (MASH).
Mechanism of Action
Dual GLP-1/glucagon receptor agonist. Glucagon component drives energy expenditure and hepatic lipid metabolism. Shows promise for MASH.
Research Protocols
For research purposes only. Not medical advice.
Research protocols use 0.6mg to 4.8mg weekly with dose escalation.
Research Notes
Clinical Research Status
Survodutide is in Phase 3 trials for obesity (SYNCHRONIZE program) and MASH (LIVERAGE program), with Boehringer Ingelheim positioning it as a differentiated metabolic therapy. Phase 2 data in obesity showed up to 18.7% body weight loss at 46 weeks with the highest dose tested. The MASH Phase 2 trial demonstrated MASH resolution without worsening fibrosis in up to 83% of patients, among the highest reported rates for any pharmacotherapy.
Key Published Findings
The Phase 2b obesity trial demonstrated dose-dependent weight loss competitive with tirzepatide at comparable timepoints. In MASH, the compound's glucagon-mediated hepatic fat reduction produced histological improvements exceeding those seen with GLP-1 monotherapy. Liver fat reduction measured by MRI-PDFF reached 70-80% relative reduction from baseline, suggesting potent hepatic-specific metabolic effects.
Safety Profile
Gastrointestinal adverse events are common during dose escalation, with nausea reported in 30-45% of patients in higher dose groups. Discontinuation rates due to adverse events were 5-10% in Phase 2, somewhat higher than GLP-1 monotherapy trials. The glucagon component has not produced clinically significant hyperglycemia, though monitoring of hepatic and cardiovascular parameters continues in ongoing trials.
Comparison to Related Compounds
Survodutide shares the GLP-1/glucagon dual mechanism with mazdutide but is differentiated by its stronger MASH development program and higher reported weight loss in Phase 2. Compared to semaglutide's MASH data, survodutide's glucagon component appears to provide superior liver fat reduction. The compound's dual approach may offer advantages over pure GLP-1 agonism for patients with concurrent obesity and liver disease.
Community Observations
Hepatologists view survodutide as one of the most promising pharmacotherapies for MASH given the unmet need and limited approved treatments. The combination of substantial weight loss with direct hepatic fat-reducing effects via glucagon agonism addresses both drivers of MASH progression. Researchers note that the GLP-1/glucagon ratio engineering is critical to maintaining glucose safety while maximizing hepatic and metabolic benefits.
Half Life
~5 days
Reconstitution
Bacteriostatic water (BAC)
Storage
Lyophilized
Refrigerate 2-8C. Protect from light.
Reconstituted
Refrigerate 2-8C. Use within 28 days.
US Legal Status
Also Known As
Latest Research
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