Research Peptide · For laboratory research use only
Also known as Triple Agonist
WBR-3R is a single synthetic peptide with agonist activity at three class B G protein-coupled receptors: the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R)1.
Its discovery and preclinical characterisation, including in vitro receptor pharmacology and studies in obese mice, were published in 20221. It has since been examined in independent rodent models of diet-induced obesity and metabolic dysfunction-associated steatohepatitis (MASH)6, and has been the subject of registered clinical trials3,4,5.
As described in the research literature
As described in the research literature, in vitro pharmacology reported balanced activity at GCGR and GLP-1R, with greater activity at GIPR1. In obese mouse studies, the authors attributed the observed body weight changes to a combination of GIPR and GLP-1R-driven reductions in calorie intake and GCGR-mediated increases in energy expenditure1.
Lipolytic function in response to GIP and to the compound has been measured in differentiated primary human adipocytes, and the protocol for that assay has been published separately2. An independent study in diet-induced obese MASH mouse and hamster models examined body composition, food and water intake, energy expenditure, insulin resistance indices, plasma lipids and hepatic lipid content6.
What published studies have examined
The discovery paper characterised activity at GCGR, GIPR and GLP-1R in vitro and compared the relative potency at each receptor1. Human adipocyte lipolysis assays have also been used to compare responses to GIP and to the compound2.
Studies in obese mice examined body weight, glycaemic control and energy expenditure1. Independent work in diet-induced obese MASH mouse and hamster models examined fat and lean mass, food preference, insulin resistance, plasma lipids and hepatic triglyceride content6.
A phase 1b trial was designed with safety and tolerability as its primary outcome, with pharmacokinetics and pharmacodynamics as secondary outcomes (NCT04143802)3. A phase 2 trial in adults with obesity used percentage change in body weight at 24 weeks as its primary end point (NCT04881760)4, and a phase 2 trial in type 2 diabetes used change in HbA1c at 24 weeks as its primary endpoint (NCT04867785)5.
LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.
Coskun T, Urva S, Roell WC, et al. Cell Metabolism, 2022.
Differentiation of human subcutaneous adipocytes and measurement of lipolytic function induced by GIP or LY3437943.
Regmi A, Roell W STAR Protocols, 2023.
LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.
Urva S, Coskun T, Loh MT, et al. The Lancet, 2022.
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.
Jastreboff AM, Kaplan LM, Frías JP, et al. The New England Journal of Medicine, 2023.
Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.
Rosenstock J, Frias J, Jastreboff AM, et al. The Lancet, 2023.
Retatrutide Shows Multiple Metabolic Benefits in Diet-Induced Obese MASH Mouse and Hamster Models.
Briand F, Le Cudennec C, Grasset E, et al. Obesity, 2026.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.