Research review
Retatrutide clinical trial results, phase 2 to phase 3
Retatrutide has now been tested in two phase 2 trials and at least three phase 3 trials. Across them, weight loss rises with dose and keeps climbing well past one year, reaching 28.3% at 80 weeks in TRIUMPH-1 at 12 mg. Gastrointestinal effects and heart-rate increases also rise with dose.
Phase 2 in obesity (2023)
338 adults with obesity or overweight without diabetes were randomized to placebo or retatrutide at 1, 4, 8 or 12 mg weekly. At 48 weeks, mean weight change was about −8.7% (1 mg), −17% (4 mg), −22.8% (8 mg) and −24.2% (12 mg), versus −2.1% with placebo. At 12 mg, every participant lost at least 5% and a quarter lost 30% or more.
Phase 2 in type 2 diabetes (2023)
In 281 adults with type 2 diabetes, HbA1c fell by up to 2.02 percentage points at 36 weeks and body weight by up to 16.9%. Retatrutide outperformed dulaglutide 1.5 mg on both.
Liver fat
An MRI substudy of the obesity trial found that liver fat fell by more than 80% on average at the 8 and 12 mg doses after 48 weeks, and most participants with excess liver fat at baseline reached normal levels.
Phase 3: TRIUMPH (2026 topline)
| Trial | Population | n | Result at 80 weeks |
|---|---|---|---|
| TRIUMPH-1 | Obesity or overweight, no diabetes | 2,339 | −19.0% (4 mg), −25.9% (9 mg), −28.3% (12 mg) |
| TRIUMPH-2 | Type 2 diabetes with obesity | 1,152 | −12.7%, −19.1%, −20.8% vs −4.0% placebo |
| TRIUMPH-3 | BMI ≥35 with cardiovascular disease | 1,949 | −21.6% (9 mg), −22.6% (12 mg) vs −3.2% placebo |
In a TRIUMPH-1 extension to 104 weeks in participants with a BMI of 35 or more, mean weight loss at 12 mg reached 30.3%. These were company-announced results; full peer-reviewed publications were pending at our last review.
Safety signals
- Nausea in TRIUMPH-1 ranged from 28.6% to 42.4% across doses, versus 14.8% on placebo.
- Discontinuation for adverse events was 11.3% at 12 mg versus 4.9% on placebo.
- Heart rate rose in a dose-dependent way in phase 2, peaking around 24 weeks.
- Dysaesthesia (abnormal skin sensation) was reported, mostly mild to moderate.
- Exploratory cardiovascular analyses in TRIUMPH-3 were inconclusive, with confidence intervals crossing no effect.
Related profiles
- GIP, GLP-1 and glucagon receptor agonist Retatrutide Retatrutide is an investigational triple agonist of the GIP, GLP-1 and glucagon receptors. Human RCTs
- GIP and GLP-1 receptor agonist Tirzepatide Tirzepatide activates both the GIP and GLP-1 receptors. Approved medicine
Questions
How long until retatrutide is approved?
Lilly has said it plans to submit to the FDA in early 2027. Review typically takes about a year unless expedited.
Do people regain weight after stopping retatrutide?
Withdrawal data have not yet been published. With semaglutide and tirzepatide, most people regain a large share of lost weight within a year of stopping.
References
- Jastreboff AM, Kaplan LM, Frías JP, et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine.
- Rosenstock J, Frias J, Jastreboff AM, et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. The Lancet.
- Sanyal AJ, Kaplan LM, Frias JP, et al. (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine.
- Eli Lilly and Company (2026). TRIUMPH-1, TRIUMPH-2 and TRIUMPH-3 topline results (company announcements, May and July 2026). Press release.