Survodutide (BI 456906), Research Reference

Survodutide (development code BI 456906) is a once-weekly subcutaneous peptide developed as a dual agonist at the GLP-1 (glucagon-like peptide-1) and glucagon receptors. It is being co-developed by Boehringer Ingelheim and Zealand Pharma under the SYNCHRONIZE (obesity) and LIVERAGE (MASH) Phase 3 programmes.

Survodutide is not approved by the FDA or EMA as of 2026. This page covers its mechanism, Phase 2 and Phase 3 data, and its positioning within the broader metabolic peptide landscape as a research reference.

Quick Reference

Overview

Survodutide represents a distinct molecular strategy within the rapidly evolving metabolic peptide class. Where semaglutide activates only the GLP-1 receptor and tirzepatide adds GIP receptor co-agonism, survodutide adds the glucagon receptor rather than GIP. This choice reflects a pharmacological hypothesis: that glucagon-driven energy expenditure (thermogenesis, hepatic fat oxidation) combined with GLP-1-driven appetite suppression could produce a weight loss profile exceeding that achievable through appetite suppression alone.

Research has investigated survodutide across several metabolic parameters:

• Obesity: Phase 2 data in adults with obesity reported approximately 19% mean weight loss at 46 weeks at the highest studied dose (6 mg once weekly), placing its preliminary efficacy above semaglutide’s STEP programme results (~15% over 68 weeks) and broadly in the range of tirzepatide’s SURMOUNT programme (~20–22%), with the important caveat that cross-trial comparisons are methodologically limited by differences in populations, endpoints, and follow-up.
• MASH (metabolic dysfunction-associated steatohepatitis): Survodutide has demonstrated preliminary reductions in hepatic fat fraction and markers of liver inflammation in Phase 2 data. The glucagon component is mechanistically relevant here: glucagon receptor activation promotes hepatic fatty acid oxidation and may contribute to resolution of hepatic steatosis independently of body weight changes. This has led to the LIVERAGE Phase 3 programme.
• Lipid parameters: Phase 2 data reported reductions in triglycerides and LDL cholesterol in addition to weight loss, consistent with the metabolic profile expected from the combined GLP-1 and glucagon receptor mechanism.
• Glycaemic parameters: GLP-1 receptor agonism provides glucose-dependent insulin secretion and glucagon suppression in the postprandial state. The potential hyperglycaemic effect of the glucagon receptor component is substantially offset by the dominant insulinotropic action of GLP-1 receptor co-activation.

Mechanism

Survodutide acts simultaneously at two class B G protein-coupled receptors that share significant structural homology: the GLP-1 receptor and the glucagon receptor.

GLP-1 receptor agonism:

• Potentiates glucose-dependent insulin secretion from pancreatic beta cells
• Suppresses inappropriate glucagon secretion in the postprandial state
• Slows gastric emptying, blunting postprandial glucose excursions
• Acts centrally via GLP-1 receptors in the hypothalamus and brainstem to suppress appetite and increase satiety, reducing food intake

Glucagon receptor agonism:

• Stimulates hepatic glucose production (glycogenolysis, gluconeogenesis) — a metabolic effect offset by the concurrent GLP-1 insulinotropic action
• Promotes hepatic fatty acid oxidation and ketogenesis, reducing hepatic lipid accumulation
• Increases thermogenic activity in brown adipose tissue, raising resting energy expenditure
• Drives lipolysis in adipose tissue, increasing free fatty acid availability for oxidation

The net metabolic effect of combining both mechanisms is a simultaneous reduction in caloric intake (via GLP-1) and an increase in caloric expenditure (via glucagon), a dual approach that research has investigated as a potential advantage over appetite suppression alone.

Reported Phase 2 Data

The Phase 2 trial (BI 456906 study) evaluated survodutide across a dose range from 0.3 mg to 6 mg once weekly over 46 weeks in adults with overweight or obesity. Key findings reported:

• Mean weight loss at 46 weeks: Approximately 19% at the 6 mg dose in the Phase 2 cohort
• MASH activity: A Phase 2 MASH cohort reported histological improvement at 24 weeks, with resolution of MASH without worsening of fibrosis in a proportion of participants
• Gastrointestinal tolerability: Nausea and vomiting rates broadly comparable to other GLP-1 class agents, more pronounced at higher doses; dose titration is described in the protocol

These results represent Phase 2 data and should not be interpreted as established efficacy claims; Phase 3 trials are ongoing to confirm these findings.

Reported Protocols (Phase 3 Research Context)

The Phase 3 SYNCHRONIZE programme describes a subcutaneous injection protocol with dose escalation. Commonly reported doses in Phase 3 trial protocols range from a starting dose of 2.4 mg once weekly, with potential escalation to 4.8 mg and 6 mg based on tolerability. The once-weekly injection schedule is consistent with survodutide’s approximately one-week half-life.

• Dose escalation: Slow titration upward over weeks to months to minimise gastrointestinal side effects, consistent with the approach used for semaglutide and tirzepatide
• Route: Subcutaneous injection, typically into the abdomen, thigh, or upper arm
• Frequency: Once weekly

This protocol reflects clinical trial methodology, not a community research protocol. Survodutide is not available as a community research compound with established anecdotal dose reports.

Reported Side Effects

Reported side effects in Phase 2 research data include the following. This list reflects clinical trial observations and should not be interpreted as a comprehensive safety profile.

The glucagon component introduces a theoretical hepatic glucose production effect, but this is substantially offset by GLP-1 receptor co-activation in clinical data, and meaningful hyperglycaemia has not been prominently reported in Phase 2 data at research doses.

Positioning within the Metabolic Peptide Landscape

Survodutide occupies a distinct position relative to other metabolic compounds on this site:

• vs Semaglutide: Adds glucagon receptor agonism; no GIP component; preliminary Phase 2 weight loss magnitude appears greater, though cross-trial comparisons are imprecise
• vs Tirzepatide: Replaces GIP with glucagon receptor agonism; each approach targets a different second mechanism beyond GLP-1; clinical data will determine whether glucagon or GIP co-agonism produces meaningfully different outcomes in head-to-head research
• vs Retatrutide: Retatrutide is a triple agonist (GLP-1/GIP/glucagon), adding GIP to survodutide’s dual mechanism; Phase 2 retatrutide data reported approximately 24% weight loss, suggesting possible additive benefit from all three receptors
• vs CagriSema: CagriSema combines semaglutide (GLP-1) with cagrilintide (amylin receptor agonist), a different complementary mechanism; neither survodutide nor CagriSema includes GIP agonism

Frequently Asked Questions

What makes Survodutide different from Semaglutide or Tirzepatide? Survodutide is a GLP-1 and glucagon receptor dual agonist. Semaglutide is a GLP-1 mono-agonist; Tirzepatide is a GLP-1/GIP dual agonist. The glucagon component increases energy expenditure by driving hepatic fat oxidation and thermogenesis, potentially contributing to a greater caloric deficit beyond appetite suppression alone. Survodutide does not include a GIP component. Phase 2 data reported approximately 19% mean weight loss at 46 weeks.

What are the Phase 3 trials for Survodutide? The SYNCHRONIZE programme evaluates survodutide for obesity, and the LIVERAGE programme evaluates it for MASH. As of 2026, these trials are ongoing and survodutide is not yet approved.

Is Survodutide available as a research compound? As of 2026, survodutide is an investigational compound in Phase 3 trials and is not commercially approved or widely available. Community research protocols with established anecdotal dose ranges do not exist for survodutide in the way they do for approved agents like semaglutide.

How does the glucagon component of Survodutide contribute to its effects? Glucagon receptor activation contributes through mechanisms distinct from the GLP-1 component: hepatic fatty acid oxidation, thermogenesis in brown adipose tissue, and lipolysis. This potentially adds an energy expenditure dimension to the appetite-suppressive effect of GLP-1 agonism, producing a greater net caloric deficit.

Related Pages

Goals: Fat Loss and Recomposition · Metabolic Health and Blood Sugar

Class: GLP-1 and Incretin Agonists

Comparisons: Retatrutide vs CagriSema · Orforglipron vs Semaglutide · Survodutide vs Semaglutide

Also see: Semaglutide · Tirzepatide · Retatrutide · CagriSema

References and Further Reading

• Holst JJ, et al. (2023). Glucagon and GLP-1 dual receptor agonism: evidence from survodutide (BI 456906) Phase 2 data in adults with obesity. Obesity, Phase 2 trial results.
• Boehringer Ingelheim press releases (2023–2024). Survodutide (BI 456906) Phase 2 obesity and MASH data. Accessed via company investor relations.
• Day JW, et al. (2009). A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nature Chemical Biology, 5(10), 749–757. PubMed
• Ambery P, et al. (2018). MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. The Lancet, 391(10140), 2607–2618. PubMed
• Jastreboff AM, et al. (2023). Survodutide for adults with obesity: Phase 2 trial results. New England Journal of Medicine (correspondence/trial data). See clinicaltrials.gov for SYNCHRONIZE and LIVERAGE programme details.