Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial.
W Timothy Garvey, Jamy Ard, Lisa Connery et al.
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In 30 seconds
This multicentre, randomised, double-blind, placebo-controlled phase 2 trial assessed once-weekly petrelintide in adults with obesity or overweight with hypertension or dyslipidaemia, without type 2 diabetes. Among 485 participants who received at least one dose, mean bodyweight change at week 28 ranged from -7·9% to -9·8% across petrelintide doses, compared with -1·7% with placebo. The largest estimated treatment difference versus placebo was -8·1% (-9·7 to -6·5) with 5·0 mg. Weight continued to decline through week 42; nausea was more common with petrelintide.
Key findings
- At week 28, bodyweight changed by -9·8% with petrelintide 5·0 mg versus -1·7% with placebo.
- The estimated treatment difference for petrelintide 5·0 mg versus placebo was -8·1% (-9·7 to -6·5).
- Weight reductions reached up to -10·7% with petrelintide by week 42.
- Nausea occurred in 79 (20%) of 404 petrelintide-treated participants versus five (6%) participants receiving placebo.
Why it matters
Obesity treatment options with mechanisms distinct from incretin-based therapies are of interest. This trial found substantial weight reduction over 28 weeks with petrelintide compared with placebo, while identifying nausea—predominantly mild during dose escalation—as a tolerability consideration. The findings provide phase 2 evidence to inform further evaluation, but do not establish long-term effectiveness or safety.
What to keep in mind
Follow-up was limited to 42 weeks, and the trial excluded people with type 2 diabetes. The abstract reports that 86% of participants were White, which may limit generalisability to more diverse populations.