The short answer
A 2023 trial helped explain the interest in retatrutide: substantial average weight loss, alongside side effects and unanswered longer-term questions.
Who took part?
Researchers randomly assigned 338 adults with obesity, or overweight plus a weight-related condition, to weekly retatrutide or placebo for 48 weeks. This was a phase 2 study, designed to explore doses before larger trials.
Percent of starting weight
Original chart based on the study. Values are reported group averages.
| Group or measure | Average result |
|---|---|
| Retatrutide 1 mg | −8.7% |
| Retatrutide 4 mg, combined | −17.1% |
| Retatrutide 8 mg, combined | −22.8% |
| Retatrutide 12 mg | −24.2% |
| Placebo | −2.1% |
What changed?
At 48 weeks, average weight change was −8.7%, −17.1%, −22.8% and −24.2% across the 1 mg, combined 4 mg, combined 8 mg and 12 mg groups, versus −2.1% with placebo. The main endpoint was earlier, at 24 weeks; these are the later results.
Digestive side effects were most common, generally mild or moderate and related to dose. Heart rate increased in a dose-related pattern, peaking at 24 weeks before declining.
What does it mean?
This trial compared retatrutide with placebo, not semaglutide or tirzepatide. It cannot establish which medicine works best. The larger TRIUMPH-1 trial provides later evidence.
Retatrutide remains investigational as of October 2026.
Sources
Jastreboff and colleagues, New England Journal of Medicine, 2023. Funded by Eli Lilly. Paper · Current development status.