Phase 1
Early human studies focused on safety, tolerability, pharmacokinetics and dose response. These studies established the basis for later dose-ranging trials.
Clinical-development timeline
Retatrutide (LY3437943) is Eli Lilly's investigational triple receptor agonist targeting GIP, GLP-1 and glucagon receptors. Its development has progressed from early safety and dose-finding work through large Phase 3 programmes.
Phase 2 — Obesity
The published 48-week Phase 2 obesity study reported mean weight changes of −8.7% at 1 mg, −17.1% at 4 mg, −22.8% at 8 mg and −24.2% at 12 mg, versus −2.1% with placebo. The most common adverse events were gastrointestinal and dose-related.
TRIUMPH-1
Phase 3 obesity/overweight without diabetes: average weight reductions at 80 weeks of 19.0% (4 mg), 25.9% (9 mg) and 28.3% (12 mg). A 104-week extension in participants with baseline BMI ≥35 reported 30.3% average reduction with 12 mg.
TRIUMPH-2
Phase 3 obesity/overweight with type 2 diabetes: average weight reductions at 80 weeks of 12.7%, 19.1% and 20.8% at 4, 9 and 12 mg respectively, with A1C reductions of up to 1.6 percentage points.
TRIUMPH-3
Phase 3 severe obesity with established cardiovascular disease: average weight loss up to 22.6% at 80 weeks. Cardiovascular event analyses were reported but do not establish cardiovascular benefit.
TRIUMPH-4
Phase 3 obesity/overweight with knee osteoarthritis: Lilly reported average weight reduction up to 28.7% at 68 weeks with substantial improvement in WOMAC knee-pain scores.
TRANSCEND-T2D-1
Phase 3 type 2 diabetes: Lilly reported average A1C reductions of 1.7–2.0 percentage points at 40 weeks and average weight reduction up to 16.8% at 12 mg.
Further Phase 3 studies
The wider programme includes additional obesity and diabetes studies, including investigations of dose-escalation strategies. Some studies remain ongoing, so the evidence base continues to develop.