Retatrutide's first phase 3 trial lowers A1C up to 1.94% and body weight up to 15.3% in type 2 diabetes

TRANSCEND-T2D-1, the first phase 3 trial of retatrutide, was published in The Lancet in June 2026. Retatrutide is an investigational once-weekly injectable that activates three receptors at once — GIP, GLP-1, and glucagon — one more than the dual agonist tirzepatide.

The 40-week, double-blind trial randomised 537 adults with type 2 diabetes inadequately controlled by diet and exercise (baseline A1C 7.0–9.5%, BMI at least 23) to retatrutide 4 mg, 9 mg, or 12 mg, or placebo. The primary endpoint, change in A1C at 40 weeks, fell by 1.69%, 1.86%, and 1.94% across the three doses versus 0.81% with placebo.

Body weight, a secondary endpoint, dropped by 11.5%, 13.9%, and 15.3% on the three doses versus 2.6% with placebo, with no plateau observed by week 40. Reported reductions extended to triglycerides, non-HDL cholesterol, systolic blood pressure, and waist circumference.

The most frequent adverse events were mild-to-moderate gastrointestinal effects — nausea, diarrhoea, vomiting — that generally eased over time. Discontinuations due to adverse events occurred in 2–5% of retatrutide participants versus none on placebo, and no severe hypoglycaemia was reported. Retatrutide remains investigational and is not approved for any use; these are single-trial results in a defined diabetes population, not evidence of long-term safety.