Petrelintide, an amylin analogue, gives 6-8% placebo-adjusted weight loss at 28 weeks

Design

Phase 2, randomised 5:1, double-blind, placebo-controlled, 32 sites

Population

493 adults with obesity or overweight with comorbidity, without type 2 diabetes

Primary outcome

Percentage change in body weight at 28 weeks

Effect

Placebo-adjusted -6.2% (95% CI -7.9 to -4.5) at 1.0 mg to -8.1% (-9.7 to -6.5) at 5.0 mg

ZUPREME 1 was a phase 2, double-blind, placebo-controlled trial across 32 sites in Poland, Romania and the USA. It randomised 493 adults with obesity, or overweight with hypertension or dyslipidaemia, and without type 2 diabetes, 5:1 to once-weekly petrelintide at one of five maintenance doses (1.0 to 9.0 mg) or placebo for 42 weeks. Mean baseline BMI was 36.7 kg/m2 and 86% were White.

At 28 weeks, weight fell 7.9% to 9.8% with petrelintide against 1.7% with placebo, a placebo-adjusted difference of 6.2% to 8.1%. Doses above 5.0 mg added little. Weight was still falling at 42 weeks, reaching up to 10.7%. Nausea, mostly mild and during dose escalation, affected 20% on petrelintide against 6% on placebo; vomiting was 3% against 6%.

Amylin analogues act on satiety through a different pathway from GLP-1 receptor agonists. The tolerability profile is the interesting part. The weight loss is smaller than with current incretin drugs, and this is a phase 2 trial in people without diabetes, funded by the manufacturer. It is not a reason to change any prescription.

• Petrelintide is investigational and not approved by the FDA, EMA or CDSCO.
• Placebo-adjusted weight loss at 28 weeks was 6.2% to 8.1% across doses, with little gain above 5.0 mg.
• Nausea affected 1 in 5 on treatment; vomiting was no more common than on placebo.
• People with type 2 diabetes were excluded, so these results do not apply to them yet.

Why it matters

Gastrointestinal side effects, not efficacy, are why many patients stop GLP-1 drugs, and this class may trade some weight loss for tolerability.

Don't overread it

This is a 28-week phase 2 trial with no head-to-head comparison against a GLP-1 drug.

The statistics, in plain English

Each dose's confidence interval for the difference from placebo stays well clear of zero, so the weight loss is not a chance finding. The intervals for the 5, 7 and 9 mg doses overlap heavily, which is why higher doses cannot be said to work better. Vomiting being lower than placebo (3% vs 6%) rests on small numbers in the 81-person placebo group.

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