Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist, for People with Type 2 Diabetes: A Randomised, Double-Blind, Placebo and Active-Comparator-Controlled, Parallel-Group, Phase 2 Trial

While the obesity trial garnered the most attention, this parallel Phase 2 study by Rosenstock, Frias, Rodbard, and colleagues, published in The Lancet, evaluated retatrutide specifically in patients with type 2 diabetes — a population that typically shows more modest weight loss responses to anti-obesity medications.

The randomized, double-blind trial enrolled adults with type 2 diabetes inadequately controlled on metformin alone. Participants were assigned to various doses of retatrutide, placebo, or the active comparator dulaglutide 1.5 mg (a standard GLP-1 receptor agonist). The study ran for 36 weeks with the primary endpoint of HbA1c change from baseline.

Retatrutide demonstrated dose-dependent improvements in both glycemic control and body weight. At the highest dose, HbA1c decreased by up to 2.02% from baseline, significantly outperforming both placebo and the active comparator dulaglutide. Body weight reductions reached 16.9% at the highest dose — an impressive result in a diabetic population where achieving double-digit weight loss has historically been challenging.

The safety profile was consistent with the incretin drug class, with gastrointestinal events being the most common side effects. These were generally mild to moderate and decreased over time. The trial confirmed that retatrutide's triple-receptor mechanism delivers meaningful benefits across both pillars of metabolic disease — hyperglycemia and obesity — potentially offering a unified treatment approach for patients with type 2 diabetes and excess weight.