Mechanism
GIP and glucagon co-agonists
These single peptides activate the GLP-1 receptor together with one or two related receptors: the GIP receptor, the glucagon receptor, or both. Tirzepatide's label describes combined GIP and GLP-1 receptor activation as enhancing insulin secretion and lowering glucagon in a glucose-dependent manner. Developers describe glucagon receptor activity as adding energy expenditure in mice and acting directly on the liver to increase fatty acid oxidation and inhibit fat production. Most of these molecules carry a fatty-acid or glycolipid side chain to extend their half-life.
How the members differ
- Tirzepatide and VK2735 combine GLP-1 and GIP receptor activity; tirzepatide is FDA-approved, while VK2735's receptor-binding data come from unpublished sponsor reports.
- Mazdutide, survodutide and pemvidutide combine GLP-1 and glucagon receptor activity; mazdutide is approved in China, and pemvidutide is described as having closely matched potency at both receptors.
- Retatrutide acts at all three receptors, with in vitro activity described as balanced at the glucagon and GLP-1 receptors and relatively higher at the GIP receptor.
- Survodutide and pemvidutide have been studied in biopsy-confirmed MASH, reflecting the liver rationale given for glucagon receptor activity.
Compounds in this group
TirzepatideHuman trial evidence · FDA-approvedTirzepatide is a once-weekly peptide that activates both the GIP and GLP-1 receptors and is approved by the FDA for type 2 diabetes (Mounjaro), and for chronic weight management and obstructive sleep apnea in adults with obesity (Zepbound). Randomized phase 3 trials have studied its effects on glycemic control, body weight and sleep apnea severity, with gastrointestinal events the most commonly reported adverse reactions. This entry summarizes the FDA labels and published trials for research reference only.
VK2735Human trial evidence · InvestigationalVK2735 is an investigational peptide that activates both the GLP-1 and GIP receptors and is being studied as a once-weekly injection and as an oral formulation. One 13-week phase 2 randomized trial has been published, and phase 3 trials are under way. It is not an approved medicine, and this entry is for research information only.
RetatrutideHuman trial evidence · InvestigationalRetatrutide is an investigational peptide that acts on three receptors (glucagon, GIP and GLP-1) and is given by weekly subcutaneous injection in clinical trials. Published phase 2 and 2026 phase 3 randomized trials have reported large mean body-weight reductions and HbA1c reductions versus placebo, with gastrointestinal events the most commonly reported adverse events. It is not approved for any use, and this entry summarizes the published and registered trials for research reference only.
MazdutideHuman trial evidence · Approved outside the USMazdutide is a once-weekly peptide that activates both the GLP-1 and glucagon receptors. It was approved in China in June 2025 for long-term weight management and in September 2025 for glycaemic control in type 2 diabetes, and it remains investigational in the United States, where phase 2 trials have been run. Randomized trials have reported body-weight and HbA1c reductions versus placebo or dulaglutide, with gastrointestinal events the most common adverse events; this entry summarizes them for research reference only.
SurvodutideHuman trial evidence · InvestigationalSurvodutide (BI 456906) is an investigational once-weekly peptide that activates both the glucagon and GLP-1 receptors. It has been studied in phase 2 and phase 3 randomized trials in obesity, type 2 diabetes and fatty liver disease. It is not an approved medicine, and this entry is for research information only.
PemvidutideHuman trial evidence · InvestigationalPemvidutide (ALT-801) is an investigational once-weekly peptide that activates both the GLP-1 and glucagon receptors with closely matched potency. It has been studied in randomized placebo-controlled trials in fatty liver disease, and a phase 3 trial in MASH was registered in 2026. It is not an approved medicine, and this entry is for research information only.
Compare Tirzepatide, VK2735, Retatrutide side by side
For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. Mechanism descriptions summarize published research and are not claims of effect in people.