- Lilly's TRANSCEND-T2D-1 was a 40-week Phase 3, randomized, double-blind, placebo-controlled trial of once-weekly retatrutide (GIP/GLP-1/glucagon triple agonist) in adults with T2D (n=537; mean diabetes duration 2.5 years; baseline A1C 7.9%).
- At 40 weeks (efficacy estimand) A1C reductions were −1.7% (4 mg), −2.0% (9 mg) and −1.9% (12 mg) versus −0.8% for placebo, and weight changes were −11.5%, −15.5% and −16.8% (−11.1, −15.1 and −16.6 kg) versus −2.5% for placebo, with no weight-loss plateau through week 40.
- Dosing started at 2 mg weekly with stepwise increases every 4 weeks to reach 4, 9 or 12 mg; the TRANSCEND program began in 2024, TRANSCEND-T2D-1 randomized 537, the program has enrolled >2,050 participants, and further results (including an ADA presentation in June) are expected over the next year.
Trial design
TRANSCEND-T2D-1 was a 40-week, randomized, double-blind, placebo-controlled Phase 3 study (n=537) in adults with T2D and inadequate glycemic control on diet and exercise; mean diabetes duration 2.5 years, baseline A1C 7.9% and baseline weight 96.9 kg (BMI 35.8 kg/m2); eligibility included A1C 7.0–9.5%, BMI ≥23 kg/m2, no antihyperglycemic meds for ≥90 days and insulin-naïve except prior gestational use.
Efficacy
At 40 weeks (efficacy estimand) mean A1C reductions were −1.7% (4 mg), −2.0% (9 mg) and −1.9% (12 mg) versus −0.8% for placebo; mean weight changes were −11.5% (−11.1 kg), −15.5% (−15.1 kg) and −16.8% (−16.6 kg) versus −2.5% (−2.8 kg) for placebo, with weight loss continuing through week 40; reductions in non‑HDL cholesterol, triglycerides and systolic blood pressure were also observed (controlled for family‑wise error for doses >4 mg).
Safety
Most common adverse events were gastrointestinal and occurred mainly during dose escalation: nausea (16.4%, 19.5%, 26.5% vs 3.7% placebo), diarrhea (18.7%, 26.3%, 22.8% vs 4.5%), vomiting (15.7%, 15.0%, 17.6% vs 2.2%); dysesthesia was reported in 4.5%, 2.3% and 4.4% versus 0% and was generally mild with most events resolving; discontinuations due to adverse events were 2.2%, 4.5% and 5.1% versus 0% for placebo.
Dosing and program
Treatment began at 2 mg once weekly with stepwise increases every four weeks to targets of 4, 9 or 12 mg; the TRANSCEND program began in 2024, has enrolled >2,050 participants, and additional data and publications, including an ADA presentation in June, are expected over the next year.
