Survodutide (BI 456906)
Once-weekly glucagon and GLP-1 receptor dual agonist (BI 456906, Boehringer Ingelheim) in phase 3 for obesity and MASH; not approved.
60-Second Scientific Briefing
Survodutide (BI 456906) is an investigational once-weekly peptide from Boehringer Ingelheim that activates the glucagon and GLP-1 receptors. It is not approved anywhere. In the phase 3 SYNCHRONIZE-1 trial (NEJM 2026, 725 adults with obesity without diabetes) mean weight change at 76 weeks was −12.2% and −13.0% with the two doses, against −5.4% with placebo. A phase 2 trial in MASH (fatty-liver inflammation) reported histological improvement in 43–62% vs 14% with placebo.
What is Survodutide?
Pharmacological Classification & Molecular IdentitySurvodutide (BI 456906) is an investigational once-weekly injectable peptide from Boehringer Ingelheim that activates the glucagon and GLP-1 receptors. It is studied for obesity and for metabolic dysfunction-associated steatohepatitis (MASH). [1] N Engl J Med, 2026 ↗
Verified Chemical & Regulatory Registry Identifiers
Mechanism of Action & Receptor Targets
Biological Pathway and Target BindingReceptor Selectivity: Agonist at the glucagon receptor and the GLP-1 receptor. GLP-1 receptor activation reduces appetite; glucagon receptor activation is studied for its effects on energy expenditure and liver fat, which is why the compound is also tested in MASH. [1] N Engl J Med, 2024 ↗ [2] Lancet Diabetes Endocrinol, 2024 ↗
Regulatory & FDA Approval Status
Legal and Regulatory ClassificationsInvestigational and not approved by the US FDA or any other regulator. Phase 3 trials (SYNCHRONIZE programme) are reporting; the first, SYNCHRONIZE-1, was published in 2026. [1] N Engl J Med, 2026 ↗
Survodutide is not approved for commercial sale, prescription therapy, or compounded medication distribution. It exists strictly within authorized scientific and clinical research frameworks.
Human Evidence & Clinical Trials
Clinical Study Readouts and Evidence SynthesesSYNCHRONIZE-1 (NEJM 2026): phase 3, 725 adults with obesity without diabetes (mean BMI 37.9), two survodutide doses vs placebo for 76 weeks; mean weight change −12.2% and −13.0% vs −5.4%, and 72.6% and 71.9% vs 46.3% lost at least 5%. Phase 2 obesity (Lancet Diabetes Endocrinol 2024): 386 adults treated for 46 weeks; weight change from −6.2% at the lowest to −14.9% at the highest dose vs −2.8% with placebo. Phase 2 MASH (NEJM 2024): 293 adults with biopsy-confirmed MASH and fibrosis F1–F3 for 48 weeks; MASH improvement without worsening fibrosis in 47%, 62% and 43% across three doses vs 14% with placebo, and fibrosis improvement by at least one stage in 34–36% vs 22%. [1] N Engl J Med, 2026 ↗ [2] N Engl J Med, 2024 ↗ [3] Lancet Diabetes Endocrinol, 2024 ↗
Clinical Evidence
SYNCHRONIZE-1 (NEJM 2026): phase 3, 725 adults with obesity without diabetes (mean BMI 37.9), two survodutide doses vs placebo for 76 weeks; mean weight change −12.2% and −13.0% vs −5.4%, and 72.6% and 71.9% vs 46.3% lost at least 5%. Phase 2 obesity (Lancet Diabetes Endocrinol 2024): 386 adults treated for 46 weeks; weight change from −6.2% at the lowest to −14.9% at the highest dose vs −2.8% with placebo. Phase 2 MASH (NEJM 2024): 293 adults with biopsy-confirmed MASH and fibrosis F1–F3 for 48 weeks; MASH improvement without worsening fibrosis in 47%, 62% and 43% across three doses vs 14% with placebo, and fibrosis improvement by at least one stage in 34–36% vs 22%.
Safety Profile & Clinical Limitations
Documented Adverse Events and Known UncertaintiesGastrointestinal adverse events dominate and are dose-related. SYNCHRONIZE-1: gastrointestinal symptoms, typically mild to moderate, in 80.9% and 89.7% vs 47.9% with placebo; no deaths. Phase 2 obesity: gastrointestinal events in 75% vs 42%. Phase 2 MASH: nausea 66% vs 23%, diarrhoea 49% vs 23%, vomiting 41% vs 4%; serious adverse events 8% vs 7%. [1] N Engl J Med, 2026 ↗ [2] N Engl J Med, 2024 ↗ [3] Lancet Diabetes Endocrinol, 2024 ↗
Cardiovascular outcomes are being tested in the SYNCHRONIZE-CVOT trial. Long-term safety, effects after stopping, and the phase 3 MASH results have not yet been published. [1] ClinicalTrials.gov ↗
Dose Approval Status
Commercial Dosing Status and Policy DirectivesNo dose is approved. The dose groups used in the trials are part of each trial's design and are described in the linked publications; they are not a recommendation. [1] ClinicalTrials.gov ↗
Under Egypt Peptides medical governance policies, no personal dosages, titration intervals, cycles, stacking recommendations, or self-injection instructions may be provided for unapproved investigational compounds. Clinical study protocols represent controlled experimental research parameters exclusively.
What is Known vs. What is Unknown
Evidence Comparison and Clinical Evidence Boundaries✓ Confirmed Scientific Evidence
- Survodutide (BI 456906) is an investigational once-weekly injectable peptide from Boehringer Ingelheim that activates the glucagon and GLP-1 receptors. It is studied for obesity and for metabolic dysfunction-associated steatohepatitis (MASH).
- Targets & Selectivity: Agonist at the glucagon receptor and the GLP-1 receptor. GLP-1 receptor activation reduces appetite; glucagon receptor activation is studied for its effects on energy expenditure and liver fat, which is why the compound is also tested in MASH.
- SYNCHRONIZE-1 (NEJM 2026): phase 3, 725 adults with obesity without diabetes (mean BMI 37.9), two survodutide doses vs placebo for 76 weeks; mean weight change −12.2% and −13.0% vs −5.4%, and 72.6% and 71.9% vs 46.3% lost at least 5%. Phase 2 obesity (Lancet Diabetes Endocrinol 2024): 386 adults treated for 46 weeks; weight change from −6.2% at the lowest to −14.9% at the highest dose vs −2.8% with placebo. Phase 2 MASH (NEJM 2024): 293 adults with biopsy-confirmed MASH and fibrosis F1–F3 for 48 weeks; MASH improvement without worsening fibrosis in 47%, 62% and 43% across three doses vs 14% with placebo, and fibrosis improvement by at least one stage in 34–36% vs 22%.
- Safety considerations: Gastrointestinal adverse events dominate and are dose-related. SYNCHRONIZE-1: gastrointestinal symptoms, typically mild to moderate, in 80.9% and 89.7% vs 47.9% with placebo; no deaths. Phase 2 obesity: gastrointestinal events in 75% vs 42%. Phase 2 MASH: nausea 66% vs 23%, diarrhoea 49% vs 23%, vomiting 41% vs 4%; serious adverse events 8% vs 7%.
? Unknown / Under Ongoing Investigation
- Cardiovascular outcomes are being tested in the SYNCHRONIZE-CVOT trial. Long-term safety, effects after stopping, and the phase 3 MASH results have not yet been published.
Verified Questions & Answers
10 Verified scientific answers with permanent anchor keysSurvodutide (BI 456906) is an investigational once-weekly injectable peptide from Boehringer Ingelheim that activates the glucagon and GLP-1 receptors. It is studied for obesity and for MASH (fatty-liver inflammation).
- Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1) (N Engl J Med, 2026-08-20)
- Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a dose-finding phase 2 trial (Lancet Diabetes Endocrinol, 2024-03-01)
It is an agonist at the glucagon and GLP-1 receptors. GLP-1 activation reduces appetite; glucagon activation is studied for effects on energy expenditure and liver fat.
- A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis (N Engl J Med, 2024-07-25)
- Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a dose-finding phase 2 trial (Lancet Diabetes Endocrinol, 2024-03-01)
No. Survodutide is investigational and not approved by the US FDA or any other regulator. Phase 3 trials are reporting.
- Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1) (N Engl J Med, 2026-08-20)
SYNCHRONIZE-1 (NEJM 2026, 725 adults without diabetes): −12.2% and −13.0% vs −5.4% with placebo at 76 weeks. Phase 2 in MASH (NEJM 2024): histological improvement in 43–62% vs 14% with placebo.
SYNCHRONIZE-1 (NEJM 2026): 725 adults with obesity without diabetes (mean age 47.1, mean BMI 37.9, mean weight 108.8 kg) were randomised to one of two survodutide doses or placebo for 76 weeks; mean weight change was −12.2%, −13.0% and −5.4%, and 72.6%, 71.9% and 46.3% lost at least 5%. Phase 2 obesity (Lancet Diabetes Endocrinol 2024): 386 adults without diabetes were treated for 46 weeks (20 weeks of dose escalation, 26 of maintenance) with four doses or placebo; weight change ranged from −6.2% at the lowest dose to −14.9% at the highest, vs −2.8% with placebo, and 60.4% completed treatment. Phase 2 MASH (NEJM 2024): 293 adults with biopsy-confirmed MASH and fibrosis stage F1–F3 received one of three doses or placebo for 48 weeks; MASH improved without worsening of fibrosis in 47%, 62% and 43% vs 14%, liver fat fell by at least 30% in 63%, 67% and 57% vs 14%, and fibrosis improved by at least one stage in 34%, 36% and 34% vs 22%.
- Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1) (N Engl J Med, 2026-08-20)
- A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis (N Engl J Med, 2024-07-25)
- Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a dose-finding phase 2 trial (Lancet Diabetes Endocrinol, 2024-03-01)
Mostly gastrointestinal and dose-related. In SYNCHRONIZE-1, gastrointestinal symptoms (typically mild to moderate) occurred in 80.9% and 89.7% vs 47.9% with placebo, with no deaths. In the MASH trial, nausea was 66% vs 23%, vomiting 41% vs 4%, and serious adverse events 8% vs 7%.
- Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1) (N Engl J Med, 2026-08-20)
- A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis (N Engl J Med, 2024-07-25)
- Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a dose-finding phase 2 trial (Lancet Diabetes Endocrinol, 2024-03-01)
Cardiovascular outcomes are being tested in SYNCHRONIZE-CVOT. Long-term safety, effects after stopping, and phase 3 MASH results have not been published yet.
No dose is approved. The trial dose groups are part of each trial's design and are described in the linked publications; they are not a recommendation.
There is no approved product label, so no official storage instructions exist outside the clinical trials, where the sponsor supplies the investigational product and its storage conditions.
It is not named individually on the 2026 WADA Prohibited List. Under section S0 (non-approved substances), any pharmacological substance without a current approval by a government health authority for human therapeutic use is prohibited at all times, so the investigational compound falls under S0 until it is approved. Athletes should confirm with their national anti-doping organisation.
- WADA Prohibited List (World Anti-Doping Agency)
Egypt Peptides publishes reviewed scientific reference monographs for documentation and research. The site does not give individual medical advice, preparation or injection instructions, combination protocols or off-label use instructions. Decisions about any medicine belong to the treating physician.
- Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1) (N Engl J Med, 2026-08-20)
Authoritative Sources & Literature Registry
Regulatory dossiers, clinical trial registries, and published studiesSurvodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1) ↗
https://pubmed.ncbi.nlm.nih.gov/42253238/
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis ↗
https://pubmed.ncbi.nlm.nih.gov/38847460/
Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a dose-finding phase 2 trial ↗
https://pubmed.ncbi.nlm.nih.gov/38330987/
SYNCHRONIZE-CVOT: cardiovascular safety of survodutide in people with overweight or obesity ↗
https://clinicaltrials.gov/study/NCT06077864