Research
Retatrutide phase 2: what the 2023 NEJM trial did and didn't show
Published 2026-10-11 · Last reviewed 2026-10-11 · Medical reviewer: pending assignment
Retatrutide is an investigational once-weekly injection that acts on three hormone receptors: GIP, GLP-1, and glucagon. It is not approved by the FDA or any other regulator.
In the phase 2 trial published in the New England Journal of Medicine in 2023, 338 adults with obesity or overweight (without diabetes) were randomized to placebo or one of several doses. At 48 weeks, mean weight change was −2.1% with placebo and −24.2% with 12 mg; the primary endpoint was week 24 (−17.5% with 12 mg).
Important limits: the trial was a phase 2 dose-finding study lasting 48 weeks and was not designed to establish long-term safety or clinical outcomes. Longer-term results depend on the phase 3 program.
The most common side effects were gastrointestinal, dose-related and mostly mild to moderate. Dose-dependent heart-rate increases were also reported, peaking at week 24 and then declining (NEJM 2023).