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The Peptide Effect
phase 3Weight Loss & Liver Disease

Survodutide

Also known as: BI 456906

Survodutide is an investigational dual glucagon/GLP-1 receptor agonist developed by Boehringer Ingelheim and Zealand Pharma. Unlike tirzepatide (which targets GIP/GLP-1), survodutide pairs GLP-1 with glucagon receptor activation to increase energy expenditure and drive hepatic fat reduction. In phase 2 trials, it achieved up to 19% weight loss and showed particularly promising results for metabolic dysfunction-associated steatohepatitis (MASH), potentially positioning it as a differentiated treatment for both obesity and liver disease.

Key Facts

Mechanism
Survodutide is a dual agonist that activates both glucagon-like peptide-1 (GLP-1) and glucagon receptors. The GLP-1 component suppresses appetite, enhances glucose-dependent insulin secretion, and slows gastric emptying — mechanisms shared with semaglutide and tirzepatide. The glucagon receptor activation adds a distinct metabolic dimension: it increases hepatic energy expenditure, stimulates fat oxidation in the liver, promotes hepatic lipid mobilization, and enhances thermogenesis. This glucagon-mediated liver-targeting effect makes survodutide particularly promising for MASH (formerly NASH), where liver fat accumulation drives disease progression.
Research Status
phase 3
Half-Life
~5-7 days (estimated from dosing interval)
Molecular Formula
C₂₁₂H₃₃₈N₅₈O₆₃S
Primary Use
Weight Loss & Liver Disease
Table of Contents

Benefits

  • Weight loss up to 18.7% body weight at 46 weeks in phase 2 obesity trialmoderate
  • Significant liver fat reduction — up to 87% relative reduction in hepatic fat fractionmoderate
  • MASH resolution without worsening fibrosis in a substantial proportion of patientsmoderate
  • Increased energy expenditure via glucagon receptor activation (addresses both sides of energy balance)preliminary
  • Improvements in metabolic parameters including triglycerides, ALT, and inflammatory markerspreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection (phase 2 — obesity)0.6 mg → 2.4 mg → 4.8 mg → 6.0 mgOnce weeklyDose escalation over 16-20 weeks in clinical trials. The 4.8 mg and 6.0 mg doses showed the greatest weight loss. Final dosing for commercial use pending phase 3 results.
Subcutaneous injection (phase 2 — MASH)2.4 mg, 4.8 mg, or 6.0 mgOnce weeklyMASH-specific trials used similar dose ranges. Liver fat reduction and MASH resolution were observed across dose levels with a dose-response relationship.
Subcutaneous injection (dose titration schedule)0.3 mg starting dose, escalating every 4 weeksOnce weeklySlow titration is critical to managing GI side effects. Injected in abdomen, thigh, or upper arm. Clinical trial protocols varied in escalation speed.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Nausea (most frequent, dose-dependent)common
  • Diarrheacommon
  • Vomiting, primarily during dose escalationcommon
  • Decreased appetitecommon
  • Transient increases in heart rate (glucagon-mediated)rare
  • Potential hyperglycemic effect from glucagon activation (mitigated by GLP-1 component in practice)rare
  • Long-term safety profile not yet established (phase 3 ongoing)serious

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Frequently Asked Questions

What is the difference between a dual and triple agonist (survodutide vs retatrutide)?
Survodutide is a dual agonist targeting GLP-1 and glucagon receptors, while retatrutide is a triple agonist targeting GIP, GLP-1, and glucagon receptors. The key difference is that retatrutide includes GIP receptor activation (which enhances insulin sensitivity and fat metabolism), while survodutide pairs GLP-1 specifically with glucagon (which increases energy expenditure and liver fat mobilization). Both include the glucagon component that distinguishes them from tirzepatide, but they have different receptor profiles that may lead to different efficacy patterns and side effect profiles.
Is survodutide primarily a weight loss drug or a liver disease treatment?
Survodutide is being developed for both indications. Boehringer Ingelheim is running phase 3 trials in obesity (SYNCHRONIZE program) and MASH/NASH. Its glucagon receptor agonism makes it particularly well-suited for liver disease because glucagon directly promotes hepatic lipid mobilization and fat oxidation. It could become the first drug to effectively treat both obesity and MASH in a single medication. However, phase 3 results will determine which indication(s) receive FDA approval. This is not medical advice.
When will survodutide be available?
Survodutide is in phase 3 clinical trials as of 2025-2026. Based on typical development timelines, FDA approval could come in 2027-2028 if phase 3 results are positive. Boehringer Ingelheim has indicated that MASH and obesity are both priority indications. The timeline could be affected by trial enrollment speed, FDA review processes, and competitive dynamics in the GLP-1 market. Monitor clinicaltrials.gov and Boehringer Ingelheim press releases for updates. This is speculative and not a guarantee.
How does survodutide compare to tirzepatide for weight loss?
In their respective phase 2 trials, tirzepatide achieved ~21% weight loss while survodutide achieved ~19%. However, cross-trial comparisons are unreliable due to differences in patient populations, trial design, and dose optimization. The key differentiator is their receptor profiles: tirzepatide targets GIP/GLP-1 while survodutide targets glucagon/GLP-1. Survodutide's glucagon component may provide advantages in liver fat reduction and energy expenditure. Head-to-head trials would be needed for a definitive comparison.
Does the glucagon component of survodutide raise blood sugar?
Glucagon is known to raise blood glucose by stimulating hepatic glucose output. However, in survodutide, the concurrent GLP-1 receptor activation counterbalances this effect through enhanced insulin secretion and glucagon suppression from alpha cells. In clinical trials, survodutide improved glycemic control in patients with type 2 diabetes rather than worsening it. The ratio of GLP-1 to glucagon activity is carefully engineered to maintain metabolic benefit while harnessing glucagon's energy expenditure effects.

References

  1. 1
    Survodutide, a dual glucagon/GLP-1 receptor agonist, for people with overweight or obesity: a randomised, double-blind, placebo-controlled, phase 2 trial(2023)PubMed ↗
  2. 2
    Efficacy and safety of survodutide in patients with NASH: a phase 2, randomised, double-blind, placebo-controlled trial(2024)PubMed ↗
  3. 3
    Glucagon and GLP-1 receptor dual agonism for the treatment of obesity and NASH(2022)PubMed ↗
  4. 4
    BI 456906: a novel glucagon/GLP-1 receptor co-agonist — pharmacological characterization and first-in-human data(2022)PubMed ↗

Last updated: 2026-02-14