What it is
Retatrutide is an experimental Lilly peptide that imitates three hormones at once: GIP, GLP-1 and glucagon. The first two are the same targets as tirzepatide. Adding glucagon is meant to raise energy expenditure and clear fat from the liver. In Lilly’s main Phase 3 obesity trial, the highest dose produced an average weight loss of about 28% over 80 weeks, according to the company.
It is not approved anywhere. It exists only inside clinical trials. Anything sold under this name outside a trial is not the product being tested.
Retatrutide (LY3437943) is a single-chain synthetic peptide derived from a GIP scaffold and lipidated with a C20 fatty diacid for albumin binding. In vitro it shows more activity at the GIP receptor than at the GLP-1 and glucagon receptors, where its activity is roughly balanced (Coskun et al., 2022). Glucagon receptor agonism is intended to increase hepatic fatty acid oxidation and energy expenditure, while GLP-1 and GIP agonism suppress appetite and blunt glucagon-driven hyperglycaemia. In obese mice, glucagon-receptor-driven increases in energy expenditure added to the intake reduction from GIP and GLP-1 agonism. Its half-life in Phase 1 was about 6 days, supporting once-weekly dosing.
Who made it and when
Lilly’s peptide group, again including Tamer Coskun, published the molecule in 2022. Phase 2 results came out in 2023 and the Phase 3 program, called TRIUMPH, started the same year. The first Phase 3 readout came in December 2025, the main obesity trial in May 2026, and the diabetes and heart-disease trials in July 2026. Lilly has said it plans to file for US approval in the first quarter of 2027.
Coskun and colleagues described the design and preclinical pharmacology in Cell Metabolism in 2022. Phase 2 obesity (n=338) and type 2 diabetes (n=281) trials read out in 2023. The TRIUMPH program comprises TRIUMPH-1 (obesity, with knee osteoarthritis and sleep apnoea sub-studies), TRIUMPH-2 (obesity with T2D), TRIUMPH-3 (severe obesity with established CVD), TRIUMPH-4 (obesity with knee osteoarthritis) and additional outcome and comparator studies. Topline dates: TRIUMPH-4 2025-12-11, TRIUMPH-1 2026-05-21, TRIUMPH-2 and -3 2026-07-23. Lilly stated in July 2026 that it plans to submit to the FDA in Q1 2027. Patent filings are held by Eli Lilly.
What the data say
In the mid-stage obesity trial, people on the highest dose lost about 24% of body weight in 48 weeks and were still losing at the end. A liver sub-study showed most participants’ liver fat fell into the normal range. In Phase 3, Lilly reports average losses of about 28% at 80 weeks in people without diabetes, about 21% in people with type 2 diabetes, and about 23% in people with heart disease. None of the Phase 3 results has yet appeared in a peer-reviewed journal. The main side effects were stomach upset during dose increases, a faster heart rate and unusual skin sensations.
Phase 2 (NCT04881760): 12 mg produced −24.2% body weight at 48 weeks vs −2.1% placebo; 100% of the 8 and 12 mg groups reached 5% or greater loss. The MASLD sub-study (n=98) reported relative liver-fat reductions of −81.4% (8 mg) and −82.4% (12 mg) at 24 weeks, with normal liver fat (under 5%) in 79% and 86%. Dose-dependent heart-rate increases peaked at 24 weeks and declined thereafter. Phase 3 toplines (company disclosures, efficacy estimand): TRIUMPH-1 −28.3% at 12 mg vs −2.2% placebo at 80 weeks, and −30.3% at 104 weeks in the BMI 35 or higher extension; TRIUMPH-2 −20.8% vs −4.0% with HbA1c down 1.5–1.6 points at 9–12 mg; TRIUMPH-3 −22.6% vs −3.2%; TRIUMPH-4 −28.7% at 68 weeks. These figures remain provisional until peer-reviewed publication.
Regulatory picture
Retatrutide has no approval anywhere and Lilly had not filed for one as of its July 2026 update. The FDA states that retatrutide cannot legally be used in compounding and is not part of any FDA-approved drug. The agency has sent warning letters to telehealth companies, ingredient distributors and sellers of “research use” products involving retatrutide. Products sold online as “retatrutide” are unapproved drugs of unknown identity.
Retatrutide is an investigational new drug under IND. It is not a component of any approved product and has no USP monograph. FDA’s guidance page on unapproved GLP-1 drugs states that retatrutide cannot be used in compounding under federal law, so neither the 503A nor the 503B pathway is available. FDA reports warning letters to telehealth companies for marketing retatrutide directly to consumers, to active pharmaceutical ingredient distributors for selling it to compounders, to outsourcing facilities for repackaging it, and to firms selling it labelled “for research purposes”. Lilly has said it plans a US marketing submission in the first quarter of 2027 based on the TRIUMPH program.
