Survodutide

Survodutide is an investigational once-weekly peptide that activates both the glucagon and GLP-1 receptors. Developed by Boehringer Ingelheim, it has been studied in obesity and in metabolic dysfunction-associated steatohepatitis and is not approved in the US.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Survodutide, also known by its development code BI 456906, is a dual agonist of the glucagon receptor and the GLP-1 receptor. It was developed by Boehringer Ingelheim in collaboration with Zealand Pharma. The rationale for combining these activities is that GLP-1 receptor activation reduces appetite and improves glucose control, while glucagon receptor activation increases energy expenditure and fat metabolism in the liver. The combination is meant to enhance weight loss and liver fat reduction beyond GLP-1 activity alone.

Survodutide has been studied in phase 2 trials in obesity and in metabolic dysfunction-associated steatohepatitis (MASH), with phase 3 programs following. Its liver effects have attracted particular interest because glucagon acts directly on hepatocytes. It belongs to a wider class of multi-receptor incretin agonists that includes the GLP-1/GIP dual agonist tirzepatide and the triple agonist retatrutide. Survodutide is investigational and not approved in the US.

Structure

Survodutide is a synthetic peptide based on a glucagon-derived sequence, with amino acid substitutions that balance activity at the glucagon and GLP-1 receptors and improve stability. It carries a fatty acid side chain that promotes albumin binding and extends its duration of action for once-weekly dosing. The exact sequence and modifications are described in patent and scientific literature, and researchers should use those sources rather than secondary descriptions. As a lipidated peptide, it is expected to show the self-association and handling properties typical of this class.

Mechanism

Survodutide activates the GLP-1 receptor and the glucagon receptor, both class B G protein-coupled receptors. GLP-1 receptor activity enhances glucose-dependent insulin secretion, slows gastric emptying and reduces appetite. Glucagon receptor activity, mainly in the liver, increases energy expenditure, fatty acid oxidation and hepatic lipid turnover, and is thought to contribute to reductions in liver fat.

Glucagon receptor activation on its own tends to raise blood glucose, and the GLP-1 component is thought to offset this. The balance between the two activities is a central design choice for this class, and how it influences efficacy and tolerability in people is being studied in clinical trials.

Research

Metabolic dysfunction-associated steatohepatitis

A phase 2 randomized trial of survodutide in adults with MASH and liver fibrosis, published in 2024, reported that a greater proportion of participants receiving survodutide achieved improvement in MASH without worsening of fibrosis compared with placebo, the trial's primary endpoint. Liver fat reductions were also reported. These results supported advancement to phase 3 testing in MASH. Liver biopsy endpoints in such trials have known variability, and phase 3 confirmation is needed.

Obesity

Phase 2 trials in adults with obesity or overweight evaluated survodutide over several months, reporting dose-related reductions in body weight compared with placebo. Gastrointestinal adverse events, such as nausea and vomiting, were common, as with other incretin-based agents, and were influenced by dose escalation. Phase 3 trials in obesity were launched to evaluate efficacy and safety in larger populations over longer periods.

Preclinical pharmacology

In rodent models of obesity and fatty liver, survodutide reduced body weight and liver fat, with effects attributed to combined appetite suppression and increased energy expenditure. Studies compared it with selective GLP-1 receptor agonists to isolate the contribution of glucagon receptor activity. These animal studies informed the clinical development program. Results in rodents do not necessarily predict the balance of benefits and adverse effects in people.

Evidence quality

Survodutide has phase 2 evidence in MASH and obesity from randomized controlled trials and is in phase 3 development. Long-term safety, cardiovascular effects and comparative efficacy against other incretin agents remain to be established. Results should be interpreted as investigational until phase 3 data are fully published and reviewed by regulators. Comparative trials against approved agents have not yet been reported in full.

Regulatory status

Survodutide is investigational and not approved in the US. It is under development by Boehringer Ingelheim, with phase 3 trials in obesity and MASH. It is not a recognized substance for US pharmacy compounding. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

For survodutide, a certificate of analysis should confirm identity by mass spectrometry with an expected mass that includes the full lipidated side chain, and report reverse-phase HPLC purity. Important impurities include variants lacking or with altered side chains, deletion sequences, and oxidation of susceptible residues such as methionine or tryptophan if present in the sequence. Lipidated peptides can aggregate, so size-exclusion chromatography is useful. Because the molecule is investigational, published reference standards are limited, and the COA should state the sequence and modification used. Counter-ion and net peptide content should be reported.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized survodutide sealed at -20 °C or colder, protected from light and moisture, and allow vials to reach room temperature before opening. Like other lipidated incretin peptides, it can self-associate and adsorb to surfaces in solution, so gentle mixing and low-binding containers help. For lab use, keep solutions refrigerated for short-term work, aliquot for longer storage at -20 °C or below, and avoid repeated freeze-thaw cycles.

Download the Survodutide data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• Mazdutide

  Mazdutide is an investigational once-weekly peptide that activates both the GLP-1 and glucagon receptors, structurally related to the gut hormone oxyntomodulin. It has been studied in obesity and type 2 diabetes and is not approved in the US.

• Retatrutide

  Retatrutide is an investigational once-weekly peptide that activates the GIP, GLP-1 and glucagon receptors. It is not FDA-approved; Eli Lilly plans a BLA submission in Q1 2027 after phase 3 results.

• Tirzepatide

  Tirzepatide is a once-weekly peptide that activates both the GIP and GLP-1 receptors. It is FDA-approved for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound).

• Semaglutide

  Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy).

References

1. Sanyal AJ, Bedossa P, Fraessdorf M, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis. N Engl J Med. 2024. Find on PubMed
2. PubMed: all indexed literature on Survodutide
3. ClinicalTrials.gov: registered studies mentioning Survodutide