Retatrutide Phase 3: what the TRIUMPH trials found

In TRIUMPH-1, published in the New England Journal of Medicine on September 29, 2026, adults without diabetes on the highest dose of retatrutide (12 mg once a week) lost 25.0% of their body weight on average over 80 weeks, against 3.9% on placebo Studied in humans. Three other Phase 3 trials, in knee osteoarthritis, type 2 diabetes and heart disease, reported large reductions too. Retatrutide is not approved; Eli Lilly says it plans to submit it to the FDA in the first quarter of 2027.

TRIUMPH-1: obesity without diabetes

2,339 adults with obesity or overweight and at least one weight-related condition. Treatment started at 2 mg and went up every four weeks to the assigned dose.

Two ways of counting. The first column is the paper’s main result: it counts everyone who was randomized, including people who stopped. The second is the figure in Lilly’s May announcement, which estimates what happens when people stay on treatment as planned. Among participants starting with a BMI of 35 or more who continued to 104 weeks, average loss reached 30.3% on 12 mg in that second measure.

The same trial had two smaller groups. In people with knee osteoarthritis, knee pain scores fell more than on placebo, and in people with sleep apnea, breathing pauses per hour fell by roughly 23 to 34, against about 10 on placebo.

TRIUMPH-2, -3 and -4

• TRIUMPH-4, adults with obesity and knee osteoarthritis, reported in December 2025: −28.7% on 12 mg and −26.4% on 9 mg against −2.1% on placebo at 68 weeks, with lower knee-pain scores.
• TRIUMPH-2, 1,152 adults with type 2 diabetes: −20.8% on 12 mg against −4.0% on placebo at 80 weeks. A1C, a three-month average of blood sugar, fell by 1.5 points on 12 mg from a starting 7.7%.
• TRIUMPH-3, 1,949 adults with severe obesity and established heart disease: −22.6% on 12 mg against −3.2% on placebo. It also counted heart attacks, strokes and related events, but there were too few to show a difference either way.

Figures for TRIUMPH-2, -3 and -4 are from Lilly’s announcements and count people who stayed on treatment.

Side effects

Mostly digestive, and more common at higher doses. In TRIUMPH-1 at 12 mg: nausea 42.4% (placebo 14.8%), diarrhea 32.0% (13.5%), constipation 26.1% (10.9%), vomiting 25.3% (4.8%). Dysesthesia, an unusual or unpleasant skin sensation, was reported by 12.5% on 12 mg against 0.9% on placebo, and by up to 20.9% on 12 mg in TRIUMPH-4. Symptoms of low blood pressure were more common at higher doses, especially in people already taking blood-pressure medicine.

Approval timing

Lilly says it is completing the manufacturing data package for a Biologics License Application and plans to submit retatrutide to the FDA in Q1 2027. Until it is approved, retatrutide is an investigational drug. The trial schedule raised the dose every four weeks for everyone, because a trial has to treat everyone the same way.