Lilly retatrutide shows large weight loss and A1C reductions in TRIUMPH-2
- Retatrutide 12 mg produced an average 20.8% weight loss (49.6 lbs) at 80 weeks.
- Among participants with baseline BMI ≥35, retatrutide 12 mg produced an average 23.4% weight loss (60.8 lbs).
- A1C fell by up to 1.6%, with up to 40.0% of participants reaching A1C <5.7%.
- TRIUMPH-2 randomized 1,152 adults; Lilly plans to submit a BLA in Q1 2027.
Key efficacy results
In the 80‑week TRIUMPH-2 Phase 3 trial, once‑weekly retatrutide (4 mg, 9 mg, 12 mg) produced dose‑dependent weight loss of −12.7% (−13.5 kg; −29.8 lbs), −19.1% (−20.6 kg; −45.4 lbs) and −20.8% (−22.5 kg; −49.6 lbs) from an average baseline weight of 106.4 kg (234.6 lbs; BMI 38.2 kg/m²). Among participants with baseline BMI ≥35, the 12 mg dose achieved an average 23.4% (−60.8 lbs) reduction, and 59.5% of 12 mg participants no longer met obesity BMI criteria.
Glycemic control improved across doses from a baseline A1C of 7.7%, with mean reductions of −1.4% (4 mg), −1.6% (9 mg) and −1.5% (12 mg); up to 40.0% of participants reached A1C <5.7% and ~79% achieved A1C ≤6.5% at higher doses.
Cardiometabolic and safety outcomes
The 12 mg dose also reduced triglycerides by 39.5%, non‑HDL cholesterol by 19.6%, systolic blood pressure by 10.8 mmHg, waist circumference by 16.9 cm, and hsCRP by 58.3%. Common adverse events were gastrointestinal: diarrhea (33.6% at 12 mg vs 13.2% placebo), nausea (28.0% vs 8.0%), constipation (16.8% vs 9.4%) and vomiting (15.7% vs 4.2%); most were mild‑to‑moderate and resolved on treatment. Discontinuation for adverse events was 3.8% (4 mg), 11.6% (9 mg), 7.7% (12 mg) versus 4.9% for placebo.
Trial design and regulatory plan
TRIUMPH-2 randomized 1,152 participants 1:1:1:1 to retatrutide 4, 9, 12 mg or placebo, using stepwise titration and an 80‑week treatment period with a 4‑week follow‑up. Lilly plans a Biologics License Application submission in Q1 2027.
Source: Lilly