RT10 - G3-R - 10 MG - Research Use Only

Product definition

What is Retatrutide?

Retatrutide is a once-weekly triple GLP-1/GIP/glucagon receptor agonist — Phase 2 data showed 24.2% mean body weight reduction at 48 weeks, the highest result in obesity pharmacology Phase 2 trial history at publication.

Retatrutide (LY3437943; Eli Lilly) is a 39-amino-acid acylated peptide engineered for balanced tri-agonism at GLP-1R, GIPR, and the glucagon receptor (GcgR). Like tirzepatide, it uses a non-native peptide backbone and a fatty acid conjugate for albumin binding (~6-day half-life, once-weekly dosing). Unlike tirzepatide, the glucagon receptor agonism adds a third pharmacological dimension: glucagon receptor activation promotes hepatic glucose mobilization, enhances adipose tissue lipolysis, and drives thermogenesis in brown adipose tissue. The TRIUMPH Phase 2 trial (2023, NEJM) was the pivotal publication: dose-escalating retatrutide 12 mg weekly produced 24.2% weight reduction at 48 weeks in adults with obesity, a result that exceeded tirzepatide's 22.5% SURMOUNT-1 result at 72 weeks when normalized for trial duration. Phase 3 TRIUMPH trials are ongoing, making retatrutide the most advanced triple agonist in the clinical obesity pharmacology pipeline.

Research context

What does the preclinical literature say about Retatrutide?

Retatrutide was developed by Eli Lilly following the commercial and clinical success of tirzepatide, with the hypothesis that adding glucagon receptor agonism to GIP/GLP-1 co-activation would further amplify metabolic outcomes. The glucagon receptor has a complex role in metabolic biology: historically studied as a counter-regulatory hormone that raises blood glucose, its role in energy expenditure and adipose thermogenesis has become a research priority in the context of obesity pharmacology. The TRIUMPH Phase 2 trial confirmed the hypothesis: the triple agonism approach produced weight reduction that exceeded dual agonism at equivalent trial timepoints, suggesting the glucagon receptor contribution to energy expenditure is pharmacologically meaningful in the context of combined incretin receptor engagement. The research mechanistic questions driving current investigation include: (1) whether the glucagon component primarily contributes through thermogenesis in BAT, through hepatic lipid metabolism changes, or through both; (2) whether the glucagon receptor activity produces any glycemic liability that must be managed by the simultaneous GLP-1R insulinotropic action; and (3) how the three receptor pathways interact at the level of downstream signaling (cAMP) in cells that co-express multiple receptors.