An amylin analogue gave 6-8% placebo-adjusted weight loss in phase 2

Design

Phase 2, randomised (5:1), double-blind, placebo-controlled, 42 weeks

Population

485 dosed adults with BMI 30+ (or 27+ with hypertension or dyslipidaemia), no diabetes

Primary outcome

Percentage change in body weight at 28 weeks

Effect

Treatment difference -6.2% to -8.1% across doses vs placebo

ZUPREME 1 randomised 493 adults with obesity but without diabetes, 5:1, to once-weekly subcutaneous petrelintide at one of five maintenance doses (1 to 9 mg) or placebo for 42 weeks. Published in The Lancet Diabetes & Endocrinology on 29 September 2026.

At 28 weeks, weight fell 7.9% to 9.8% on petrelintide against 1.7% on placebo, a placebo-adjusted difference of 6.2 to 8.1 percentage points. Weight was still falling at 42 weeks, reaching up to 10.7%. Nausea affected 20% on active drug versus 6% on placebo, mostly mild and during dose escalation; vomiting, diarrhoea and constipation were similar between groups.

Amylin works through satiety pathways distinct from GLP-1. The weight loss here is smaller than with current incretin drugs, so the interest is tolerability and a possible combination partner rather than a replacement.

This is phase 2 in a largely White population; it is not available outside trials.

• Petrelintide is investigational and not available for prescribing anywhere
• Gastrointestinal side effects apart from nausea were close to placebo in this trial
• Weight loss at 28 weeks was below what tirzepatide and semaglutide achieve in their trials
• Patients asking about 'new injections' can be told phase 3 data are still needed

Why it matters

Obesity drugs may soon be chosen for tolerability rather than maximal weight loss alone.

Don't overread it

Phase 2, 28-week primary endpoint and no head-to-head comparison: it does not show petrelintide matches incretin drugs.

The statistics, in plain English

Each dose's confidence interval sits well below zero against placebo, so the weight loss is not chance. The doses from 5 to 9 mg overlap heavily, which suggests a plateau rather than more benefit from higher doses.

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