Evidence Grade C — Moderate human evidence. 61 published studies, 39 human. 0 registered clinical trials.
Medically reviewed by a licensed medical professional
Survodutide is a once-weekly injection in Phase III development by Boehringer Ingelheim that activates both GLP-1 and glucagon receptors. The glucagon component adds a mechanism that burns liver fat and increases energy expenditure — effects that pure GLP-1 drugs do not provide. It is being developed for both obesity and fatty liver disease (MASH).
Survodutide is also known by these brand and alternate names:
61 published studies: 39 human, 0 animal, 1 in-vitro, 31 reviews
Survodutide is in Phase III development (not yet approved). In a Phase II obesity trial (387 patients, 46 weeks), the highest planned dose achieved approximately 15% weight loss. A separate Phase II MASH trial (293 patients) showed MASH improvement without worsening fibrosis in up to 62% of patients, compared to 14% with placebo.
Phase III trials are ongoing for both obesity and MASH indications. Survodutide's dual development strategy — targeting both weight loss and liver disease — reflects the growing recognition that these conditions are closely interconnected.
Survodutide activates both the GLP-1 receptor (appetite suppression, insulin enhancement) and the glucagon receptor (energy expenditure, liver fat oxidation). The glucagon component directly stimulates the liver to burn stored fat, which is particularly relevant for MASH — a condition characterised by liver fat accumulation and inflammation. The drug is designed with a deliberate bias toward GLP-1 receptor activity.
In a Phase II obesity trial (387 patients), the highest planned dose achieved approximately 15% weight loss at 46 weeks, with head-to-head Phase II data showing superiority over semaglutide. A separate Phase II MASH trial showed improvement in liver disease without worsening scarring in up to 62% of patients (versus 14% on placebo) — among the strongest liver results for any drug in this class. Phase III trials are ongoing for both indications but no Phase III results are yet available. Key concerns include a 24.6% treatment discontinuation rate in the Phase II obesity trial and a puzzling finding where the highest MASH dose was less effective than the second-highest, requiring careful dose optimisation in Phase III. If the liver disease programme succeeds, regulatory filing could occur around 2027.
Survodutide (BI 456906) is a dual GLP-1/glucagon receptor agonist containing 29 amino acids. The fully conjugated molecular weight is 4,231.62 Da with molecular formula C192H289N47O61 (CAS 2805997-46-8). The plasma half-life is approximately 6 days, enabling once-weekly subcutaneous dosing, with more than 99% albumin binding. Position 2 contains Ac4c (1-aminocyclobutane-1-carboxylic acid) for DPP-4 resistance, and position 24 features a C18 fatty diacid via Gly-Ser-Gly-Ser-Gly-Gly-gammaGlu linker. Licensed from Zealand Pharma to Boehringer Ingelheim, which is solely responsible for global development.
Research suggests survodutide activates GLP-1R (EC50 0.33 nM) and GCGR (EC50 0.52 nM) with deliberate GLP-1R bias in human plasma. The GLP-1R component drives appetite suppression, gastric emptying delay, and glucose-dependent insulin secretion. The GCGR component increases energy expenditure (key differentiator versus GLP-1-only agonists), stimulates hepatic lipolysis and beta-oxidation for direct liver fat reduction, reduces hepatic inflammation, and exerts anti-fibrotic effects by reducing stellate cell activation. In preclinical DIO mice, survodutide achieved greater weight-lowering than maximally effective semaglutide doses.
Phase 2 obesity (le Roux et al. 2024, Lancet Diabetes Endocrinol, N=387, 46 weeks): -14.9% weight loss at 4.8 mg (planned treatment) versus -2.8% placebo; actual treatment analysis showed -18.7%. Phase 2 MASH (Sanyal et al. 2024, NEJM, N=293, 48 weeks): MASH improvement without worsening fibrosis in up to 62% versus 14% placebo (p<0.001). Phase 2 T2D (Bluher et al. 2024, N=411): HbA1c -1.71% with significantly greater weight loss than semaglutide 1.0 mg. Phase 3 program includes SYNCHRONIZE (5 obesity trials, including N=5,508 CVOT) and LIVERAGE (MASH). SYNCHRONIZE-1 topline results expected H1 2026. FDA Breakthrough Therapy Designation for MASH October 2024.
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CT-388 is in Phase II/III development (not yet approved). Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with low discontinuation rates due to adverse events (5.9%). Phase III trials are underway. The combination of high efficacy and low discontinuation rates in Phase II is notable — many obesity drugs achieve high weight loss but suffer from tolerability-driven dropouts. Roche's $2.7 billion acquisition of the developer signals significant confidence in the programme.
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This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
