Survodutide
Dual Glucagon/GLP-1 Receptor AgonistinvestigationalAlso known as: BI 456906, Glucagon/GLP-1 Dual Agonist
An investigational dual glucagon and GLP-1 receptor agonist being developed for obesity and MASH (metabolic dysfunction-associated steatohepatitis) with significant liver fat reduction.
Overview
Survodutide is an investigational peptide developed by Boehringer Ingelheim and Zealand Pharma that acts as a dual agonist of the glucagon and GLP-1 receptors. Unlike tirzepatide (GLP-1/GIP), survodutide pairs GLP-1 with glucagon receptor activation, specifically targeting hepatic fat metabolism and energy expenditure. In Phase 2 trials, survodutide demonstrated up to 18.7% weight loss at 46 weeks and remarkable liver fat reduction of up to 87% in patients with MASH. The glucagon component directly stimulates hepatic fatty acid oxidation and ketogenesis, making survodutide particularly promising for fatty liver disease. It is currently in Phase 3 trials for both obesity and MASH, with potential to be the first drug specifically designed to address the metabolic liver disease epidemic.
Mechanism of Action
Survodutide activates two receptors simultaneously: (1) GLP-1 receptor — suppresses appetite, enhances glucose-dependent insulin secretion, and slows gastric emptying; (2) Glucagon receptor — increases hepatic energy expenditure, promotes fatty acid oxidation and ketogenesis in the liver, stimulates thermogenesis, and directly reduces hepatic lipid accumulation. The glucagon-mediated hyperglycemic potential is counterbalanced by the GLP-1 component's insulin-stimulating effects. The net result is enhanced weight loss and particularly pronounced liver fat reduction compared to pure GLP-1 agonists.
Molecular Formula
Investigational (not fully disclosed)
Molecular Weight
~4000 g/mol (estimated)
Sequence
Modified peptide with dual glucagon and GLP-1 receptor binding activity (proprietary)
Dosage Protocols
Dose Range
0.6mg – 4.8mg
Frequency
Once weekly
Route
subcutaneous
Cycle Length
46 weeks (trial duration)
Phase 2 trial titrated to doses of 2.4mg, 3.6mg, or 4.8mg weekly. The 4.8mg group achieved 18.7% weight loss at 46 weeks. Slow titration required.
Source: Phase 2 clinical trial (Blüher et al., NEJM 2024)
Side Effects
| Effect | Severity |
|---|---|
| Nausea | moderate |
| Vomiting | moderate |
| Diarrhea | mild |
| Decreased appetite | mild |
| Increased heart rate | mild |
| Increased lipase/amylase | mild |
Pros & Cons
Exceptional liver fat reduction (up to 87%) — potentially transformative for MASH treatment
Strong weight loss comparable to other next-generation obesity drugs (up to 18.7%)
Glucagon component uniquely increases energy expenditure and hepatic fat oxidation
Convenient once-weekly dosing
Still investigational — not yet approved, awaiting Phase 3 results
Significant GI side effects leading to notable discontinuation rates in trials
Long-term cardiovascular and safety data not yet available
Glucagon receptor activation requires careful glycemic balance management
Research Studies
Legal Status
Investigational — not yet approved by any regulatory agency. In Phase 3 clinical trials by Boehringer Ingelheim. Not available commercially.
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