Retatrutide
Phase 3 (Eli Lilly TRIUMPH program, e.g. NCT06383390); a pre-approval expanded access program opened June 2026 for patients with severe obesity who've failed approved treatments; a Biologics License Application was planned for Q1 2027 as of mid-2026 — not yet FDA-approved.
Retatrutide is a synthetic peptide engineered as a single-molecule agonist at three receptors: GLP-1R, GIPR, and the glucagon receptor (GCGR). Combined GLP-1/GIP agonism enhances glucose-dependent ins...
Mechanism of Action
Retatrutide is a synthetic peptide engineered as a single-molecule agonist at three receptors: GLP-1R, GIPR, and the glucagon receptor (GCGR). Combined GLP-1/GIP agonism enhances glucose-dependent insulin secretion and satiety; the added glucagon receptor agonism is believed to increase energy expenditure and hepatic fat oxidation, proposed to explain the larger fat-mass reductions seen versus GLP-1-only or GLP-1/GIP dual-agonist therapies. In its Phase 2 obesity trial, the 12 mg dose produced up to 24.2% weight loss at 48 weeks versus placebo; gastrointestinal adverse events were the most common finding across trials, and a body-composition substudy found dose-dependent fat-mass reductions with relatively preserved lean mass.
