Retatrutide

Retatrutide (development code LY3437943) is Eli Lilly's investigational once-weekly subcutaneous peptide that activates three receptors at once: GLP-1, GIP, and the glucagon receptor. It belongs to a generation of multi-receptor agonists that emerged after tirzepatide (dual GLP-1 plus GIP, marketed as Mounjaro and Zepbound) showed that activating more than one incretin pathway could produce larger metabolic effects than a single GLP-1 agonist alone. Retatrutide adds the glucagon receptor on top of GLP-1 and GIP, on the rationale that glucagon agonism raises energy expenditure, with the GLP-1 component dominating appetite suppression and the GIP component contributing additional insulin and adipose effects.

The discovery and pharmacological characterisation come from Coskun and colleagues (Cell Metabolism, September 2022). That paper describes the molecule as a 39-amino-acid peptide engineered with non-standard residues for stability and a C20 fatty-diacid side chain that supports once-weekly dosing through reversible albumin binding. The early-phase clinical work in the same paper showed pharmacokinetics consistent with once-weekly subcutaneous administration and a body-weight reduction that persisted up to day 43 after a single dose.

The headline Phase 2 obesity readout came in Jastreboff et al. (NEJM, August 2023). The trial randomised 338 adults with obesity or overweight plus a weight-related condition to weekly subcutaneous retatrutide at 1 mg, 4 mg, 8 mg or 12 mg, or to placebo, for 48 weeks. The primary endpoint was percent change in body weight at 24 weeks. The 48-week results: a mean body-weight reduction of 24.2% on the 12 mg dose, 22.8% on the 8 mg dose, 17.1% on the 4 mg dose, and 8.7% on 1 mg, versus 2.1% on placebo. By the 15% weight-loss threshold, 83% of the 12 mg group, 75% of the 8 mg group and 60% of the 4 mg group reached it, versus 2% on placebo. The most common adverse events were dose-dependent gastrointestinal symptoms (nausea, vomiting, diarrhoea, constipation), mostly mild to moderate, with starting at 2 mg rather than 4 mg reducing early events. Heart rate rose dose-dependently and peaked around week 24 before declining.

The Phase 2 type-2 diabetes trial (Rosenstock et al., Lancet, August 2023) randomised 281 adults with type-2 diabetes to retatrutide at 0.5, 4, 8 or 12 mg, to dulaglutide 1.5 mg as an active comparator, or to placebo, over 36 weeks. HbA1c reductions ranged from about 0.4 percentage points on the 0.5 mg dose to about 2.0 percentage points on the 12 mg escalation arm, versus 0.0 on placebo and 1.4 on dulaglutide. Weight loss at 36 weeks reached about 17% on the 12 mg dose, versus about 3% on placebo and about 2% on dulaglutide. About 35% of retatrutide recipients reported GI adverse events; there were no severe hypoglycaemic events or deaths.

The Phase 3 programme is named TRIUMPH. TRIUMPH-1 (NCT05929066) tests retatrutide in obesity or overweight without type-2 diabetes, enrolled 2,335 participants, and has a primary completion date of April 2026. TRIUMPH-2 (NCT05929079) tests it in type-2 diabetes with obesity or overweight, about 1,000 participants, primary completion May 2026. TRIUMPH-3 (NCT05882045) tests it in obesity with established cardiovascular disease, 1,946 participants. TRIUMPH-4 (NCT05931367) tested it in obesity with knee osteoarthritis and completed in November 2025, with formal results not yet posted to the registry. TRIUMPH-5 (NCT06662383) is the head-to-head trial against tirzepatide, 800 participants. TRIUMPH-Outcomes (NCT06383390) is the cardiovascular and kidney outcomes trial, 10,000 participants, with primary completion in February 2029.

Regulatory status is consistent: no marketing authorisation anywhere we cover. The FDA has not approved retatrutide. The EMA has not authorised it; the only EMA record is a paediatric investigation plan agreed in September 2024, which is part of the development process rather than a marketing authorisation. The MHRA has not authorised it. There is no branded retatrutide product on any pharmacy shelf. The compound is investigational, accessible only through clinical trials and any expanded-access mechanism Lilly may operate in specific jurisdictions.

A practical reality worth naming: retatrutide is already appearing on grey-market and compound-pharmacy listings, ahead of any approval, any pharmacopoeial monograph and any quality framework. Regulators across our coverage area treat unauthorised retatrutide the same way they treat unauthorised semaglutide: as an unapproved medicinal product, regardless of the label on the vial. The 'research peptide' label does not change that, and the absence of a regulator-supervised supply chain for an investigational molecule is a meaningful safety concern in itself. We cover this because pretending it does not exist is unhelpful, but the position is straightforward: there is no legitimate consumer route to retatrutide today.

This page is educational. We do not advise on starting, stopping, dosing or sourcing retatrutide. Decisions about investigational compounds belong inside a clinical-trial framework. Use the regulation pages below for the jurisdiction-specific position, the FAQ for the most-asked questions, and the source list for the Phase 2 and Phase 3 trial registrations and the primary readouts.