Retatrutide: dose ranges from the trials

Published trial data for retatrutide covers two Phase 2 programmes and an active Phase 3 series, all run by Eli Lilly. The doses that appeared in those trials ranged from 0.5 mg to 12 mg administered subcutaneously once weekly.^[1] No regulatory authority has approved a dose or labelled indication for retatrutide. What follows is a summary of what investigators tested and what they reported, framed as a reading guide for those tracking the clinical literature.

Phase 2 obesity trial: 1 mg, 4 mg, 8 mg and 12 mg

The foundational efficacy dataset comes from Jastreboff et al., published in the New England Journal of Medicine in August 2023.^[1] The trial enrolled 338 adults with obesity or overweight plus at least one weight-related condition and ran for 48 weeks. Participants were randomised to weekly subcutaneous retatrutide at 1 mg, 4 mg, 8 mg or 12 mg, or to placebo.

Gastrointestinal tolerability was a known concern for the class, so the protocol built in a starting-dose approach to mitigate early nausea. Participants in the 4 mg and 8 mg arms began at a 2 mg or 4 mg lead-in dose before escalating to their target. The 12 mg arm started at 2 mg. The 1 mg arm held constant at 1 mg throughout.

Mean weight change from baseline at 48 weeks was 8.7% on 1 mg, 17.1% on 4 mg, 22.8% on 8 mg and 24.2% on the 12 mg dose, versus 2.1% on placebo.^[1] At the 15% body-weight loss threshold, the 12 mg, 8 mg and 4 mg groups reached it in 83%, 75% and 60% of participants respectively, compared with 2% on placebo. Gastrointestinal adverse events were dose-dependent, mostly mild to moderate, and more common in the groups that started at 4 mg rather than 2 mg.

Phase 2 diabetes trial: 0.5 mg, 4 mg, 8 mg and 12 mg

The second Phase 2 trial, Rosenstock et al. in the Lancet (August 2023), tested retatrutide in adults with type-2 diabetes.^[2] The trial randomised 281 participants across 36 weeks to retatrutide at 0.5 mg, 4 mg, 8 mg or 12 mg, to dulaglutide 1.5 mg as an active comparator, or to placebo. Multiple escalation sub-arms were included for the 8 mg and 12 mg groups, reflecting the team's continuing investigation of how quickly participants could ramp up to target.

HbA1c reductions at the primary endpoint (24 weeks) ranged from 0.43 percentage points on 0.5 mg to 2.02 percentage points on 12 mg, compared with 0.01 points on placebo and 1.41 points on dulaglutide.^[2] Body-weight reductions at 36 weeks ran from about 3% on 0.5 mg to about 17% on 12 mg, against roughly 3% on placebo and 2% on dulaglutide. Gastrointestinal adverse events occurred in around 35% of retatrutide recipients and there were no severe hypoglycaemic events or deaths in either Phase 2 programme.

Phase 3: the TRIUMPH programme

Eli Lilly designed the Phase 3 TRIUMPH series around two target maintenance doses, 4 mg and 12 mg, reflecting what the Phase 2 data identified as the lower useful dose and the dose with the strongest efficacy signal.^[4] All TRIUMPH trials use a weekly subcutaneous injection with a multi-step escalation period before reaching the maintenance dose.

TRIUMPH-1 (NCT05929066) is the pivotal obesity trial, enrolling 2,335 participants without type-2 diabetes, with a primary completion date of April 2026. TRIUMPH-2 (NCT05929079) covers type-2 diabetes with obesity, around 1,000 participants, primary completion May 2026.^[4] Three further studies assess specific comorbidities: TRIUMPH-3 (cardiovascular disease), TRIUMPH-4 (knee osteoarthritis, completed November 2025), and TRIUMPH-5, a head-to-head against tirzepatide in 800 participants. The cardiovascular and kidney outcomes trial, TRIUMPH-Outcomes, involves 10,000 participants with a primary completion in February 2029.

What these dose numbers are not

Reporting a trial dose range is not the same as reporting a clinically approved dose. Retatrutide has no marketing authorisation from the FDA, the EMA, the MHRA or any other regulator we cover. There is no prescribing label, no pharmacopoeial monograph and no approved route for clinicians to prescribe it outside a clinical trial or an expanded-access mechanism. Phase 2 trial results describe what investigators gave, under controlled conditions, to carefully selected participants. They do not define an optimal dose for a general population.

A 2025 systematic review of the available Phase 2 data confirmed that the 12 mg dose produced the most marked reductions in body weight, BMI and waist circumference across the trial population.^[5] That finding is an observation about the trial data, not a recommendation. The Phase 3 results will be the data set on which any regulatory submission would rest.

Where the literature stands

The Phase 2 work established proof of concept and a dose-response relationship across 0.5 mg to 12 mg weekly, with the strongest weight-loss signal at 12 mg and the lowest useful glucose-lowering signal at 0.5 mg.^[1][2] The discovery chemistry and first-in-human pharmacokinetics appeared in Coskun et al. (Cell Metabolism, 2022), which also described the once-weekly dosing rationale based on the molecule's albumin-binding half-life.^[3] The TRIUMPH Phase 3 programme is now the active data-generation front. Until primary results are published and reviewed by regulators, the dose numbers in the Phase 2 papers are the only trial-reported figures in the peer-reviewed record.

For the regulatory position in specific countries, see the retatrutide overview page, which covers the EMA paediatric investigation plan, the FDA investigational status and the absence of any approved product anywhere. This article is educational; it is not a dosing guide. Consult a healthcare professional before making any decision about investigational compounds.