Survodutide

What Is Survodutide?

Survodutide is an investigational synthetic peptide that activates two hormone receptors: the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R).^[1] It was first described in the scientific literature under the development code BI 456906.^[1]

The design follows the same dual-receptor idea as oxyntomodulin, a natural gut peptide that activates both GCGR and GLP-1R and lowers body weight in humans by increasing energy expenditure and reducing energy intake.^[1] Reviews of incretin-based drug development group survodutide with other molecules that activate the glucagon and GLP-1 receptors together, separate from GLP-1 receptor agonists such as semaglutide and from the GIP/GLP-1 co-agonist tirzepatide.^[2]

Survodutide’s clinical program has focused on two conditions: obesity and MASH, the progressive inflammatory form of metabolic dysfunction-associated steatotic liver disease.^[3][4][5]

Chemical Structure and Molecular Identity

Survodutide is a 29-residue linear peptide with a fatty-acid side chain. PubChem (CID 171378821) lists its molecular formula as C192H289N47O61 and its molecular weight as 4232 g/mol, and its CAS Registry Number is 2805997-46-8.

Structural features

• Glucagon-like backbone: positions 1 and 3 to 15 of the PubChem structure are identical to the corresponding positions of human glucagon.
• Non-coded residue: position 2 is 1-aminocyclobutane-1-carboxylic acid, a cyclic amino acid outside the standard genetic code.
• Lipidation: the side chain of lysine 24 carries an octadecanedioic (C18) fatty diacid, attached through a gamma-glutamic acid and a short glycine/serine linker.
• C-terminus: an amidated alanine.

The discovery paper describes BI 456906 as a potent acylated peptide in which the C18 fatty acid serves as the half-life-extending element.^[1] Because of the cyclobutane residue, the sequence cannot be written fully in the standard one-letter amino-acid code. PubChem also lists the synonym GLXC-27923.

Research History and Development

Survodutide’s published record runs from a 2022 preclinical characterization, through two phase 2 trials published in 2024, to a phase 3 obesity trial published in 2026.

Discovery

The 2022 discovery report characterized BI 456906 in cell-based functional assays and in acute and subchronic studies in mice, including GLP-1R knockout and transgenic reporter mice.^[1]

Phase 2

A randomized, double-blind, placebo-controlled dose-finding trial ran for 46 weeks at 43 centers in 12 countries. It enrolled 387 adults with a BMI of 27 kg/m² or higher and without diabetes, compared four dose levels with placebo, and used percent change in body weight as the primary endpoint.^[3] Of 386 treated participants, 233 (60.4%) completed the 46-week treatment period; the trial is registered as NCT04667377.^[3]

A second phase 2 trial lasted 48 weeks and enrolled adults with biopsy-confirmed MASH and fibrosis stages F1 through F3. It compared three dose levels with placebo, and 293 participants received trial medication.^[4]

Phase 3

A phase 3, double-blind trial randomized 725 adults with a BMI of 30 or higher, or 27 or higher with at least one obesity-related complication other than diabetes, to one of two survodutide regimens or placebo, alongside lifestyle counseling. Its two primary endpoints were percent change in body weight and the share of participants losing at least 5% of body weight by week 76.^[5] Participants had a mean age of 47.1 years, and 40.6% were men.^[5] A 2025 systematic review listed survodutide among the GLP-1/glucagon receptor agonists with ongoing phase 3 obesity trials.^[6]

Mechanisms Studied in Research

Survodutide is studied as one molecule that lowers body weight by two routes: reduced food intake, linked to GLP-1 receptor activity, and increased energy expenditure, linked to glucagon receptor activity. Most mechanistic data come from cell assays and mouse studies.^[1]

GLP-1 receptor engagement

In mice, GLP-1R target engagement was shown with glucose tolerance, food intake and gastric emptying tests.^[1] Dual receptor activity was further supported with GLP-1R knockout mice, transgenic reporter mice and an ex vivo bioactivity assay.^[1]

Glucagon receptor engagement

Glucagon receptor engagement in mice was tracked through liver expression of nicotinamide N-methyltransferase mRNA and through circulating biomarkers, including amino acids and fibroblast growth factor-21.^[1] The authors attributed the compound’s weight-lowering effect to the combination of higher energy expenditure and lower food intake.^[1]

Liver disease rationale

The phase 2 MASH trial was built on the hypothesis that dual glucagon and GLP-1 receptor agonism may be more effective than GLP-1 receptor agonism alone for treating MASH.^[4] Reviews of MASH therapeutics now discuss survodutide alongside GLP-1 receptor agonists and the GIP/GLP-1 co-agonist tirzepatide.^[7][8]

Key Findings From Published Studies

Published trials report that survodutide reduced body weight in adults with obesity and improved liver histology in adults with MASH and fibrosis compared with placebo, with gastrointestinal events as the most frequent adverse effects.^[5][4]

Preclinical

In mice, pharmacological doses of BI 456906 produced greater body-weight reductions than maximally effective doses of the GLP-1 receptor agonist semaglutide.^[1]

Obesity

In the phase 3 trial, participants had a mean baseline BMI of 37.9 and a mean body weight of 108.8 kg. At week 76, under the treatment-regimen estimand, mean body weight changed by −12.2% in the lower-dose group and −13.0% in the higher-dose group, compared with −5.4% with placebo.^[5]

MASH and liver fibrosis

In the phase 2 MASH trial, improvement in MASH with no worsening of fibrosis occurred in 47%, 62% and 43% of the low-, middle- and highest-dose groups, compared with 14% with placebo.^[4] A decrease in liver fat content of at least 30% occurred in 63%, 67% and 57%, versus 14%, and fibrosis improved by at least one stage in 34%, 36% and 34%, versus 22%.^[4] Nausea was more frequent with survodutide than with placebo (66% vs 23%).^[4]

Comparative analyses

A 2025 Bayesian network meta-analysis of 19 randomized trials in 29,506 adults with overweight or obesity included survodutide among the dual agonists. As a group, dual agonists produced mean weight loss of 11.0 kg, similar to retatrutide and greater than GLP-1 receptor agonists (9.0 kg), and the authors described them as having a favorable efficacy-safety balance.^[9]

For a lipidated peptide with a non-coded residue like survodutide, batch-specific HPLC and mass spectrometry certificates of analysis are the practical identity check.

Regulatory and Research Status

Survodutide is an investigational compound and is not approved by the US Food and Drug Administration (FDA). The 2026 phase 3 report describes it as an investigational glucagon receptor–GLP-1 receptor dual agonist.^[5]

Its development has reached phase 3 in obesity, and it has been tested in phase 2 in MASH with liver fibrosis.^[5][6][4] Reviewers of MASH therapeutics note open questions that apply to survodutide and other agents in advanced development, including treatment duration, variable response between patients and long-term adherence.^[8] Gastrointestinal tolerability is cited as a major concern for glucagon/GLP-1 and related agonists in this setting.^[7] A 2025 systematic review of the obesity pipeline adds that data on mortality, cardio-renal outcomes and long-term weight maintenance are still needed for the emerging incretin-based agents.^[6]

Outside registered clinical trials, survodutide is not approved for human use, and material described as survodutide is intended for laboratory research only.