Retatrutide: Two Human Phase 2 Trials, NEJM and the Lancet

In the phase 2 obesity trial published in the New England Journal of Medicine in June 2023, Jastreboff and colleagues randomised adults with a BMI of 30 or higher, or 27 to 30 with a weight-related condition, to retatrutide across a dose range or placebo. At 24 weeks the trial met its primary endpoint with mean weight reduction up to 17.5%. At 48 weeks, a secondary endpoint, mean weight reduction reached 24.2% in the highest dose group. Among participants receiving 4 mg, 92%, 75%, and 60% achieved reductions of 5%, 10%, and 15% or more respectively.

The companion phase 2 trial in type 2 diabetes, published in the Lancet in the same month by Rosenstock and colleagues, was a double-blind, placebo and active-controlled, parallel-group trial conducted in the USA. It examined glycaemic control and body weight against both placebo and dulaglutide as an active comparator, and its results informed dose selection for the phase 3 programme.

Both are human trials, in two of the highest-impact journals in medicine, published within the same month.

The compound itself, development code LY3437943, is a 39-amino-acid peptide, molecular formula C221H342N46O68, with agonist activity at three receptors: the glucose-dependent insulinotropic polypeptide receptor, the GLP-1 receptor, and the glucagon receptor. That triple-receptor design separates it from the single and dual agonists that preceded it.

Retatrutide is investigational and holds no marketing approval. Supplied for laboratory research use only.