Retatrutide is a triple agonist of the glucagon receptor (GCGR), glucagon-like peptide 1 receptor (GLP-1R), and gastric inhibitory polypeptide receptor (GIP receptor), also known as the glucose-dependent insulinotropic polypeptide receptor.[1] It induces cAMP accumulation in HEK293 cells expressing the human GCGR, GLP-1R, or GIP receptor (EC50s = 5.79, 0.775, and 0.0643 nM, respectively). Retatrutide (0.1-30 nmol/kg) decreases plasma glucose levels in an intraperitoneal glucose tolerance test in mice. It decreases body weight, calorie intake, fat mass, and lean mass in a mouse model of diet-induced obesity in a dose-dependent manner. Acute administration of retatrutide (10 nmol/kg) delays gastric emptying and chronic administration for 10 days decreases food intake and body weight in mice.[2]
References:
[1].Coskun, T., Urva, S., Roell, W.C., et al.LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of conceptCell Metab.34(9)1234-1247(2022).
[2].Urva, S., O'Farrell, L., Du, Y., et al.The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptyingDiabetes Obes. Metab.25(9)2784-2788(2023).