Lilly's retatrutide shows large weight and A1C reductions in Phase 3 TRIUMPH‑2 and TRIUMPH‑3

Topline efficacy

In TRIUMPH‑2, a Phase 3, 80‑week trial randomizing 1,152 adults with obesity or overweight and type 2 diabetes to retatrutide 4 mg, 9 mg, 12 mg or placebo, mean weight loss at 80 weeks was -12.7% (-29.8 lb), -19.1% (-45.4 lb) and -20.8% (-49.6 lb) for 4 mg, 9 mg and 12 mg respectively, versus -4.0% (-9.3 lb) for placebo. A1C reductions reached up to -1.6% from a baseline of 7.7%.

Severe obesity with cardiovascular disease

In TRIUMPH‑3, an 80‑week trial in 1,949 participants with BMI ≥35 kg/m² and established cardiovascular disease, retatrutide 9 mg and 12 mg produced mean weight losses of -21.6% (-52.7 lb) and -22.6% (-55.8 lb) at 80 weeks, versus -3.2% (-7.7 lb) for placebo.

Cardiovascular events and risk factors

Pre‑specified time‑to‑event analyses showed 44 MACE‑5 events in pooled retatrutide arms versus 52 in placebo (HR 0.82; 95% CI 0.55–1.22). For MACE‑3 the HR was 1.12 (95% CI 0.64–1.96). Additional on‑treatment analyses yielded HRs of 0.73 (MACE‑5) and 0.92 (MACE‑3). The highest dose reduced triglycerides by 37.0%, non‑HDL cholesterol by 16.5%, systolic blood pressure by 9.3 mmHg, waist circumference by 19.0 cm and hsCRP by 51.2%.

Safety and regulatory path

The most common adverse events were gastrointestinal (diarrhea, nausea, constipation) and decreased appetite; reported incidence varied by dose. Discontinuation rates for adverse events ranged from 3.8% to 13.5% across retatrutide doses versus about 4.8–4.9% for placebo. Lilly is completing CMC data and plans to submit a Biologics License Application for retatrutide in Q1 2027.