Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide.

Plain Language Summary

Cryo-EM or crystallography study revealing the molecular structural basis for retatrutide's simultaneous activation of GLP-1R, GIPR, and GCGR. Identifies the binding modes, receptor conformational changes, and structural features that enable a single peptide molecule to potently activate three distinct G protein-coupled receptors. Provides the mechanistic structural foundation explaining retatrutide's superior weight loss compared to dual agonists.