Survodutide

Key Benefits#

• Up to 18.7% body weight reduction at 46 weeks (Phase 2)
• Strong MASH activity — Phase 3 SYNCHRONIZE-NASH trials ongoing
• Reduces hepatic fat content via glucagon receptor-driven liver oxidation
• Once-weekly subcutaneous injection
• Greater weight loss potential than GLP-1 monotherapy
• Improvements in liver fibrosis markers in early data

Mechanism of Action#

Survodutide activates GLP-1 receptors to suppress appetite and slow gastric emptying while simultaneously activating glucagon receptors to increase energy expenditure and promote hepatic fat oxidation. The glucagon arm is particularly beneficial in MASH, where it stimulates liver-specific beta-oxidation of fatty acids, reducing steatosis and inflammation. The dual mechanism yields weight loss that exceeds GLP-1 monotherapy and uniquely addresses both metabolic and hepatic disease.

Dosing Protocols#

Side Effects#

• Nausea (most common during titration)
• Vomiting
• Diarrhea
• Decreased appetite
• Heart rate increase (glucagon receptor effect)
• Injection site reactions
• Potential hypoglycemia in combination with insulin

Contraindications#

Not FDA approved — investigational. Personal or family history of medullary thyroid carcinoma or MEN2. Pregnancy.

Storage#

Refrigerate at 2–8°C. Protect from light. Do not freeze.

1. 1.
   Optimization of patient and site engagement in the SYNCHRONIZE™ phase 3 clinical trial program for survodutide in obesity through clinical trial simulation

   Rubino DM, Mooney V, van de Walle V, Baanstra D, Daniëls W, Recaldin C et al. · Contemporary clinical trials communications · 2026PubMed Verified

2. 2.
   Survodutide acts through circumventricular organs in the brain and activates neuronal regions associated with appetite regulation

   Zimmermann T, Bleymehl K, Haebel P, Perens J, Roostalu U, Hecksher-Sørensen J et al. · Molecular metabolism · 2026PubMed Verified

3. 3.
   IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes

   Elmendorf AJ, Yousefian M, Kim IM, Hardaway JA, Habegger K, Flak JN · Pharmacological research · 2026ReviewPubMed Verified

4. 4.
   Comparative Analysis of Glucagon Receptor Agonists vs. Resmetirom in MASLD and MASH: Network Meta-Analysis of Clinical Trials

   Andonie CR, Abusalameh A, Ismail I, Hodrob T, Ladadweh M, Ayesh H · Endocrinology, diabetes & metabolism · 2026Meta-AnalysisPubMed Verified

5. 5.
   Operationalising disease modification in obesity trials: A blueprint based on the SYNCHRONIZE-1 survodutide study

   Wang B, Huang J, Chen Z · Diabetes, obesity & metabolism · 2026PubMed Verified

6. 6.
   Hepatic GCGR is required for the superior weight loss and metabolic effects of a structurally related analogue of the dual GCGR/GLP-1R agonist survodutide in mice

   Long F, Challa TD, Efthymiou V, Klug M, Klein T, Neubauer H et al. · Diabetes, obesity & metabolism · 2026PubMed Verified

7. 7.
   Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed

   Martínez-Castelao A, Górriz JL, Fernández-Fernández B, Soler MJ, Navarro-González JF · Journal of clinical medicine · 2025ReviewPubMed Verified

8. 8.
   Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon

   Abdelrahman RM, Musa TH, Arbab IA, Suliman MH, Ahmed EO, Mohamed AN et al. · Journal of obesity · 2025ReviewPubMed Verified

9. 9.
   Survodutide for the Treatment of Obesity: Baseline Characteristics of the SYNCHRONIZE Cardiovascular Outcomes Trial

   Platz E, Kaplan LM, le Roux CW, Wharton S, Burger S, Hussain SA et al. · JACC. Heart failure · 2025PubMed Verified

10. 10.
    Baseline characteristics in the SYNCHRONIZE™-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes

    Wharton S, le Roux CW, Bozkurt B, Platz E, Bleckert G, Ajaz Hussain S et al. · Diabetes, obesity & metabolism · 2026RCTPubMed Verified

11. 11.
    Selective amylin receptor agonism: promise beyond incretins

    van Beek AP · Lancet (London, England) · 2025PubMed Verified

12. 12.
    Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1)

    le Roux CW, Wharton S, Bozkurt B, Platz E, Bleckert G, Ajaz Hussain S et al. · Diabetes, obesity & metabolism · 2026RCTPubMed Verified

13. 13.
    Histological efficacy of anti-diabetic agents in MASH and the mediating role of weight loss: A network meta-analysis

    Banerjee M, Pal R, Pal S · Diabetes, obesity & metabolism · 2026Meta-AnalysisPubMed Verified

14. 14.
    Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity

    Son JW, le Roux CW, Blüher M, Nauck MA, Lim S · Endocrine reviews · 2025PubMed Verified

15. 15.
    Shared mechanistic pathways of glucagon signalling: Unlocking its potential for treating obesity, metabolic dysfunction-associated steatotic liver disease, and other cardio-kidney-metabolic conditions

    Neff GW · Diabetes, obesity & metabolism · 2025ReviewPubMed Verified

16. 16.
    Survodutide: A Dual GLP-1/Glucagon Agonist Reshaping Cardiometabolic Care

    Arun AJ, Darji B, Baig M, Frishman WH, Aronow WS · Cardiology in review · 2025PubMed Verified

17. 17.
    Efficacy and safety of survodutide on glycemic control and weight loss in adults: A systematic review and meta-analysis

    Xiao YJ, Yu S, Zhang YL, Chen J, Liu YQ, Liu XL et al. · Diabetes, obesity & metabolism · 2025Meta-AnalysisPubMed Verified

18. 18.
    Weight management treatment in obesity

    Rubio-Herrera MA, Mera-Carreiro S · Medicina clinica · 2025ReviewPubMed Verified

19. 19.
    Safety Choice Drivers of the Coming Treatment Options for Non-Cirrhotic Metabolic Steatohepatitis

    Mangia A, Valenti LVC · Liver international : official journal of the International Association for the Study of the Liver · 2025ReviewPubMed Verified

20. 20.
    Efficacy of Dual Glucagon and Glucagon-like Peptide-1 Receptor Agonists Across the Cardiometabolic Continuum: A Review of Current Clinical Evidence

    Stachteas P, Nasoufidou A, Karakasis P, Koiliari M, Karagiannidis E, Koufakis T et al. · Reviews in cardiovascular medicine · 2025ReviewPubMed Verified

21. 21.
    Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit With GLP-1/Glucagon Agonism

    Doiron JE, Elbatreek MH, Xia H, Yu X, Gehred ND, Gromova T et al. · JACC. Basic to translational science · 2025PubMed Verified

22. 22.
    Review: Special Issue: Real-world evidence on the use of GLP1 receptor agonists: Emerging concepts in obesity management: focus on glucagon receptor agonist combinations

    Anderson SL · Drugs in context · 2025ReviewPubMed Verified

23. 23.
    Efficacy and Safety of Twincretin Survodutide, a Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist as an Anti-Obesity and Anti-Diabetes Medication: A Systematic Review and Meta-Analysis

    Dutta D, Kamrul-Hasan ABM, Joshi A, Dhall A, Nagendra L, Sharma M · Indian journal of endocrinology and metabolism · 2025ReviewPubMed Verified

24. 24.
    Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA

    Sinha B, Ghosal S · Obesity (Silver Spring, Md.) · 2025Meta-AnalysisPubMed Verified

25. 25.
    Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease

    Muzurović E, Haluzik M, Horváth L, Vlacho B, Mauricio D · Current pharmaceutical design · 2025PubMed Verified

26. 26.
    Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide

    Augustin R, Oldenburger A, Baader-Pagler T, Zimmermann T, Borghardt J, Hecksher-Sørensen J et al. · Molecular metabolism · 2025PubMed Verified

27. 27.
    Therapeutic horizons in metabolic dysfunction-associated steatohepatitis

    Newsome PN, Loomba R · The Journal of clinical investigation · 2025ReviewPubMed Verified

28. 28.
    Survodutide: a novel peptide for treatment of obesity and metabolic diseases

    Vinton TY · Proceedings (Baylor University. Medical Center) · 2025PubMed Verified

29. 29.
    Evaluating the efficacy and safety of survodutide for obesity: a systematic review and meta-analysis of randomized controlled trials

    Awad AA, Abdrabou Abouelmagd A, Mohammed F, Elettreby AM, Mahmoud Marey M, Aldemerdash MA et al. · Proceedings (Baylor University. Medical Center) · 2025PubMed Verified

30. 30.
    Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis

    Wang Y, Zhou Y, Wang Z, Ni Y, Prud'homme GJ, Wang Q · The Journal of clinical endocrinology and metabolism · 2025Meta-AnalysisPubMed Verified

31. 31.
    Review Article: GLP-1 Receptor Agonists and Glucagon/GIP/GLP-1 Receptor Dual or Triple Agonists-Mechanism of Action and Emerging Therapeutic Landscape in MASLD

    Zafer M, Tavaglione F, Romero-Gómez M, Loomba R · Alimentary pharmacology & therapeutics · 2025ReviewPubMed Verified

32. 32.
    Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities

    Bailey CJ, Flatt PR, Conlon JM · Peptides · 2025ReviewPubMed Verified

33. 33.
    The pleiotropic effects of glucagon-like peptide-1 receptor agonists in patients with metabolic dysfunction-associated steatohepatitis: a review for gastroenterologists

    Alkhouri N, Charlton M, Gray M, Noureddin M · Expert opinion on investigational drugs · 2025ReviewPubMed Verified

34. 34.
    Emerging pharmacotherapies for obesity: A systematic review

    Kokkorakis M, Chakhtoura M, Rhayem C, Al Rifai J, Ghezzawi M, Valenzuela-Vallejo L et al. · Pharmacological reviews · 2025Meta-AnalysisPubMed Verified

35. 35.
    Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis

    Souza M, Al-Sharif L, Antunes VLJ, Huang DQ, Loomba R · Hepatology (Baltimore, Md.) · 2025Meta-AnalysisPubMed Verified

36. 36.
    Subgroup analysis by sex and baseline BMI in people with a BMI ≥27 kg/m(2) in the phase 2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist

    le Roux CW, Steen O, Lucas KJ, Startseva E, Unseld A, Hussain SA et al. · Diabetes, obesity & metabolism · 2025RCTPubMed Verified

37. 37.
    GLP-1, GIP/GLP-1, and GCGR/GLP-1 receptor agonists: Novel therapeutic agents for metabolic dysfunction-associated steatohepatitis

    Singh A, Sohal A, Batta A · World journal of gastroenterology · 2024ReviewPubMed Verified

38. 38.
    Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article

    Sidrak WR, Kalra S, Kalhan A · Indian journal of endocrinology and metabolism · 2024ReviewPubMed Verified

39. 39.
    Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction

    Kaya E, Yilmaz Y, Alkhouri N · Expert opinion on investigational drugs · 2024ReviewPubMed Verified

40. 40.
    Survodutide, a glucagon receptor/glucagon-like peptide-1 receptor dual agonist, improves blood pressure in adults with obesity: A post hoc analysis from a randomized, placebo-controlled, dose-finding, phase 2 trial

    le Roux CW, Steen O, Lucas KJ, Ekinci EI, Startseva E, Unseld A et al. · Diabetes, obesity & metabolism · 2025PubMed Verified

41. 41.
    Effect of survodutide, a glucagon and GLP-1 receptor dual agonist, on weight loss: a meta-analysis of randomized controlled trials

    Wan H, Xu N, Wang L, Liu Y, Fatahi S, Sohouli MH et al. · Diabetology & metabolic syndrome · 2024PubMed Verified

42. 42.
    Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2)

    Wharton S, le Roux CW, Kosiborod MN, Platz E, Brueckmann M, Jastreboff AM et al. · Obesity (Silver Spring, Md.) · 2025Clinical TrialPubMed Verified

43. 43.
    The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation

    Stefanakis K, Kokkorakis M, Mantzoros CS · Metabolism: clinical and experimental · 2024ReviewPubMed Verified

44. 44.
    Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial

    Kosiborod MN, Platz E, Wharton S, le Roux CW, Brueckmann M, Ajaz Hussain S et al. · JACC. Heart failure · 2024Clinical TrialPubMed Verified

45. 45.
    Glucagon and glucagon-like peptide-1 dual agonist therapy: A possible future towards fatty kidney disease

    Kanbay M, Copur S, Guldan M, Ozbek L, Mallamaci F, Zoccali C · European journal of clinical investigation · 2025ReviewPubMed Verified

46. 46.
    JPEN Journal Club 88. Determining the hypothesis of a study

    Koretz RL · JPEN. Journal of parenteral and enteral nutrition · 2025PubMed Verified

47. 47.
    Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit with GLP-1/Glucagon Agonism

    Doiron JE, Elbatreek MH, Xia H, Yu X, Gehred ND, Gromova T et al. · bioRxiv : the preprint server for biology · 2025PubMed Verified

48. 48.
    Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis

    Lawitz EJ, Fraessdorf M, Neff GW, Schattenberg JM, Noureddin M, Alkhouri N et al. · Journal of hepatology · 2024Clinical TrialPubMed Verified

49. 49.
    A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis

    Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E et al. · The New England journal of medicine · 2024RCTPubMed Verified

50. 50.
    Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity

    Drucker DJ · Diabetes care · 2024ReviewPubMed Verified