Retatrutide – ushering in the era of “triple receptor agonists” for weight loss?

Studies showed that, with weekly administration, at week 24, overweight/obese non-diabetic subjects in the retatrutide 12mg group experienced a mean weight loss of 18.7 kg (17.5%); in the secondary endpoint, the retatrutide 12mg group achieved a mean weight loss of 26.2 kg (24.2%) at the end of week 48 treatment.

Retatrutide is a triple agonist peptide of the glucagon receptor (GCGR), glucose-dependent insulinotropic peptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). Retatrutide has a half-life of approximately 6 days and is administered once weekly.

Compared to endogenous receptor ligands, retatrutide has weaker effects on human GCG and GLP-1 receptors (0.3-fold and 0.4-fold, respectively), but stronger effects on human GLP-1 receptors (8.9-fold).