Retatrutide

Eli Lilly (investigational)

Retatrutide is a 39-amino-acid synthetic peptide engineered as a simultaneous agonist at three metabolic receptors: GIP, GLP-1, and glucagon. The addition of glucagon-receptor agonism to the incretin-dual framework (tirzepatide's mechanism) is the novel element. Glucagon elevates hepatic and adipose energy expenditure — previously a hazardous direction pharmacologically, because glucagon also raises blood glucose, but when balanced against potent GLP-1 and GIP agonism, the net effect appears to be enhanced fat oxidation with neutral-to-improved glycemic control. The phase-2 obesity trial (Jastreboff et al., 2023) reported a mean 24.2% reduction in body weight at 48 weeks at the 12 mg weekly dose — exceeding tirzepatide's 20% magnitude at 72 weeks and setting a new benchmark for pharmacologic weight loss. Trial-reported adverse events were GI-dominated and qualitatively similar to GLP-1 and GIP/GLP-1 agents. Phase-3 TRIUMPH trial program is ongoing as of 2026; FDA approval is anticipated if phase-3 data replicate. Retatrutide is not yet approved or available commercially. Any product sold under its name via research-peptide channels is investigational-supply or grey-market and should be treated with significantly elevated caution until phase-3 safety data reads out.