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Survodutide

Investigational dual glucagon/GLP-1 receptor agonist studied for obesity and MASH liver disease

Half-life

~4 days (approx 100 hours)

Typical Dose

0.6-6mg weekly (titrated up over 20-24 weeks)

Format

Injectable

Purity

≥98%

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Overview

Survodutide (BI 456906) is an investigational once-weekly dual receptor agonist that activates both the glucagon receptor and the GLP-1 receptor [1,4]. Developed by Boehringer Ingelheim in partnership with Zealand Pharma, it is not approved by the FDA, EMA, or any other regulator and remains in Phase 3 testing [1]. The GLP-1 arm curbs appetite while the glucagon arm is intended to raise energy expenditure and mobilise liver fat [4]. In a 387-person Phase 2 obesity trial, the 4.8mg dose produced up to 18.7% mean body weight reduction at 46 weeks versus roughly 2% on placebo [1]. A separate 293-participant Phase 2 trial in metabolic dysfunction-associated steatohepatitis (MASH) showed histological improvement in up to 62% of participants [2], and dual agonism also lowered HbA1c in a Phase 2 diabetes study that used semaglutide as an active comparator [3].

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Mechanism

Dual agonism of the glucagon receptor (GCGR) and the GLP-1 receptor [4,5]. GLP-1 activation slows gastric emptying and reduces food intake, while glucagon receptor activation drives hepatic lipid mobilisation and increased energy expenditure [4]. In preclinical work, survodutide produced greater weight loss than maximally dosed semaglutide in mice, an effect attributed to the added energy-expenditure component [4]. Boehringer used circulating biomarkers such as FGF-21 and amino acid shifts to confirm glucagon receptor engagement in humans and to select the clinical dose [5]. Unlike Retatrutide, survodutide does not engage the GIP receptor [1,4].

Researched benefits

  • Up to ~18.7% mean weight loss at the top dose in Phase 2 (46 weeks)
  • Dual glucagon and GLP-1 receptor activation
  • MASH improvement without worsening fibrosis in up to 62% (Phase 2)
  • Glucagon component adds energy expenditure beyond appetite suppression
  • Once-weekly subcutaneous dosing

Frequently asked

What is Survodutide?

Survodutide (BI 456906) is an investigational dual receptor agonist that activates both the glucagon receptor and the GLP-1 receptor once weekly. It is being developed by Boehringer Ingelheim and Zealand Pharma for obesity and MASH. Unlike single-target GLP-1 drugs, the glucagon component is meant to increase energy expenditure on top of appetite suppression.

How much weight loss did Survodutide produce?

In the 387-person Phase 2 dose-finding trial (le Roux 2024, Lancet Diabetes & Endocrinology), the 4.8mg dose produced up to 18.7% mean body weight reduction at 46 weeks versus about 2% on placebo, and 55% of that group lost at least 15% of body weight. Dosing had not plateaued at trial end, so the ceiling is not yet established.

What did the MASH liver trial show?

In a 293-participant Phase 2 trial (Sanyal 2024, New England Journal of Medicine), survodutide improved MASH without worsening fibrosis in up to 62% of participants at the 4.8mg dose versus 14% on placebo, and improved fibrosis by at least one stage in up to 36%. The data earned FDA Breakthrough Therapy designation for MASH.

Survodutide vs Retatrutide?

Both go beyond plain GLP-1, but the mechanisms differ. Survodutide is a dual glucagon/GLP-1 agonist, while retatrutide is a triple agonist that adds GIP. Retatrutide has reported higher Phase 2 weight loss (~24% at 48 weeks), but survodutide has stronger published liver (MASH) outcomes. Both remain investigational and neither is approved.

Is Survodutide approved?

No. Survodutide is investigational and not approved by the FDA, EMA, or any other regulator. It is in Phase 3 development, including the SYNCHRONIZE obesity program and the LIVERAGE MASH program. It is available for research purposes only.

What is the half-life and how is it dosed?

Survodutide has a half-life of roughly 100 hours (about 4 days), consistent with once-weekly subcutaneous dosing. Phase 2 trials used slow escalation over 20-24 weeks up to 4.8mg or 6mg weekly to limit gastrointestinal side effects, which were the most common adverse events and mirrored the profile of GLP-1 agonists.

Scientific Literature

References

  1. [1]

    le Roux CW, Steen O, Lucas KJ, et al. (2024). Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.

    The Lancet Diabetes & Endocrinology · PubMed: 38330987

  2. [2]

    Sanyal AJ, Bedossa P, Fraessdorf M, et al. (2024). A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.

    New England Journal of Medicine · PubMed: 38847460

  3. [3]

    Blüher M, Rosenstock J, Hoefler J, et al. (2024). Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial.

    Diabetologia · PubMed: 38095657

  4. [4]

    Zimmermann T, Thomas L, Baader-Pagler T, et al. (2022). BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.

    Molecular Metabolism · PubMed: 36356832

  5. [5]

    Thomas L, Martel E, Rist W, et al. (2024). The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection.

    Diabetes, Obesity and Metabolism · PubMed: 38560764

Citations are provided for educational purposes. Always verify primary sources before drawing research conclusions.

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