Lilly's retatrutide shows major weight loss and benefits for diabetes, knee osteoarthritis and OSA

Overview

Lilly reported Phase 3 results for retatrutide, an investigational once‑weekly GIP/GLP‑1/glucagon triple receptor agonist, showing marked weight loss and improvements across glycemia, knee osteoarthritis pain and moderate‑to‑severe obstructive sleep apnea. TRIUMPH‑1 and TRANSCEND‑T2D‑1 data were presented at the ADA and TRANSCEND‑T2D‑1 was published in The Lancet.

Key efficacy

In TRIUMPH‑1, retatrutide 12 mg produced an average 70.3 lb (28.3%) weight loss at 80 weeks; 65.3% of participants reached BMI <30 and 33.3% reached BMI <25. Doses of 4 mg and 9 mg produced mean losses of 47.2 lb (19.0%) and 64.4 lb (25.9%) respectively. In a pre‑specified extension, participants with baseline BMI ≥35 who continued 12 mg through 104 weeks lost 85.0 lb (30.3%).

Diabetes, OA and OSA outcomes

TRANSCEND‑T2D‑1 showed A1C reductions up to 2.0% from a 7.9% baseline at 40 weeks; up to 90% achieved A1C <7.0%, up to 85% ≤6.5% and up to 46% achieved A1C <5.7%. Weight loss at 40 weeks reached 36.6 lb (16.8%) and was still trending down. In TRIUMPH‑1, WOMAC pain fell up to 4.3 points (73.1%) from a baseline of 6.0 and OSA AHI fell up to 36.1 events/hour (60.6%) from a baseline of 58.6 events/hour.

Cardiometabolic signals and safety

Retatrutide yielded reductions in triglycerides (up to 41.0%), non‑HDL cholesterol (up to 24.2%), systolic blood pressure (up to 12.3 mmHg) and waist circumference (up to 9.5 in) at 80 weeks; TRANSCEND‑T2D‑1 showed similar directional reductions at 40 weeks. Adverse events were consistent with incretin therapies—primarily nausea, diarrhea and vomiting—with some dysesthesia and urinary tract infections; most events were mild–moderate and resolved. Discontinuation rates for adverse events reached 11.3% in the TRIUMPH‑1 12 mg arm and 5.1% in the TRANSCEND‑T2D‑1 12 mg arm. TRIUMPH‑1 randomized 2,339 participants and TRANSCEND‑T2D‑1 randomized 537 participants.