A comprehensive, peer-reviewed breakdown of retatrutide (LY3437943) — the triple GLP-1/GIP/glucagon receptor agonist showing unprecedented weight loss results in Phase 2 clinical trials.
What Is Retatrutide?
Retatrutide — designated LY3437943 in clinical development — is a synthetic acylated peptide developed by Eli Lilly and Company. It functions as a simultaneous agonist at three distinct G-protein coupled receptors: GLP-1R, GIP-R, and GCGR.
Triple Receptor Mechanism of Action
Understanding retatrutide's mechanism requires appreciating how each of its three receptor targets contributes to the overall metabolic effect. The three pathways are synergistic rather than merely additive — glucagon receptor agonism increases energy expenditure while GLP-1R and GIP-R reduce intake.
Phase 2 Clinical Trial Results
The pivotal Phase 2 trial enrolled 338 adults with BMI ≥27 kg/m². Participants receiving 12mg retatrutide achieved 24.2% mean body weight reduction at 48 weeks — the largest weight loss ever documented in a peptide clinical trial.