Survodutide
clinical trialsAlso known as: BI 456906
**Mechanism of Action** Survodutide (BI 456906) is a synthetic dual agonist of the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R). By simultaneously activating both receptors, it enhances energy expenditure via glucagon-mediated thermogenesis and lipolysis while reducing appetite and delaying gastric emptying through GLP-1 signaling. This dual mechanism aims to achieve greater weight loss and metabolic improvements than selective GLP-1 agonists alone. **Key Research Findings** Phase 2 trials demonstrated significant dose-dependent weight reduction in adults with obesity, with mean losses up to 18.7% at 46 weeks (vs. 2.0% placebo). In MASH (metabolic dysfunction-associated steatohepatitis), a Phase 2 study showed 83% of patients achieving MASH resolution without worsening fibrosis at 48 weeks (vs. 18.2% placebo). Common adverse events include gastrointestinal effects (nausea, vomiting), consistent with GLP-1 agonism. Phase 3 trials (SYNCHRONIZE program) are ongoing for obesity and MASH. **Clinical Relevance** Survodutide represents a promising next-generation incretin-based therapy for obesity and MASH, potentially offering superior efficacy over selective GLP-1 agonists. Its dual mechanism may address both weight loss and liver histology endpoints. Regulatory approval decisions await Phase 3 outcomes. For research purposes only — not medical advice.
Key data
C192H289N47O61Research & studies
Pegozafermin, cilofexor + firsocostat, and denifanstat were significantly better than placebo for fibrosis regression without MASH worsening.; Pegozafermin, survodutide, and tirzepatide were the most effective for MASH resolution without worsening fibrosis.; SUCRA rankings identified pegozafermin as top for both fibrosis regression (79.92) and MASH resolution (91.75).; Eight agents significantly improved fibrosis regression, while twelve agents significantly improved MASH resolution versus placebo.
GLP-1 receptor agonists (e.g., semaglutide) achieve 15-17% weight loss with a good safety profile.; Tirzepatide, a dual GLP-1/GIP agonist, achieves up to 22.5% weight loss at highest doses.; Combinations like Cagrisema and Retatrutide are expected to achieve similar weight loss ranges.; New drugs target gastroenteropancreatic hormones to improve cardiometabolic variables.
MASH is driven by obesity and type 2 diabetes, increasing risks of cirrhosis, hepatocellular carcinoma, and liver failure.; Current regulatory approval relies on histological endpoints, with growing interest in noninvasive biomarkers and personalized approaches.; Recent trials of agents like semaglutide, tirzepatide, and resmetirom show promise in resolving MASH and improving fibrosis.; Genetic variants (e.g., PNPLA3) and artificial intelligence may enhance patient stratification and trial design.
GLP-1RAs and dual agonists (GLP-1/GIP or GLP-1/glucagon) show promise for treating MASLD/MASH.; Phase I-III trials demonstrate hepatic improvements: MASH resolution, liver fat reduction, and prevention of fibrosis progression.; Cardiometabolic benefits include improved glycemic control, weight loss, and better cardiovascular outcomes.; Potential benefits extend to comorbidities like obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, and heart failure with preserved ejection fraction.
GLP-1 receptor agonists (e.g., liraglutide, semaglutide) show efficacy in MASH management but with limited histological improvement of fibrosis.; Dual agonists like GLP-1/GIP RA (tirzepatide) and Glucagon/GLP-1 RA (survodutide) yield higher rates of MASH resolution and fibrosis improvement.; Gastrointestinal side effects are a major tolerability concern for these medications.; Future research should optimize drug regimens, identify responsive patients, and balance efficacy with tolerability.
Dual glucagon and GLP-1 receptor agonism may be more effective for weight loss than GLP-1 agonism alone, but cardiovascular effects are unknown.; SYNCHRONIZE-CVOT is a phase 3, event-driven, cardiovascular safety study of survodutide versus placebo.; The primary endpoint is time to first 5-point major adverse cardiovascular event composite.; This is the first trial to assess cardiovascular safety and efficacy of survodutide in people with obesity and increased cardiovascular risk.
Frequently asked questions
What is Survodutide?
**Mechanism of Action** Survodutide (BI 456906) is a synthetic dual agonist of the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R). By simultaneously activating both receptors, it enhances energy expenditure via glucagon-mediated thermogenesis and lipolysis while reducing appetite and delaying ga
How does Survodutide work?
Dual glucagon/GLP-1 receptor agonist in phase 3 for obesity and MASH.
What is the research status of Survodutide?
Survodutide is currently classified as clinical trials, with 67 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Survodutide?
Survodutide has a molecular weight of approximately 4232 g/mol (formula C192H289N47O61).
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