On 30 September 2026, The Lancet Diabetes & Endocrinology published the primary-endpoint analysis of ZUPREME-1, the Phase 2 trial of petrelintide (ZP8396) in adults with obesity or overweight and at least one weight-related comorbidity. Petrelintide is a long-acting, acylated amylin-receptor agonist developed by Zealand Pharma and licensed to Roche in a deal valued at up to $5.3 billion. It is an investigational research compound: it holds no marketing authorisation in the UK or anywhere else, and this article describes trial results, not a treatment.

What ZUPREME-1 reported

The trial's primary endpoint was mean change in body weight at Week 28. The middle dose performed best: 5 mg produced a mean reduction of 9.8%, against 1.7% on placebo — a placebo-adjusted reduction of 8.1%, the largest in the study. The two lowest doses, 1 mg and 2.5 mg, both produced 7.9%. Higher doses did not add efficacy: 7 mg produced 9.3% and 9 mg 9.4% at Week 28, so the dose-response curve flattened above 5 mg.

At Week 42, under the efficacy estimand, mean weight reduction reached up to 10.7%. Under the more conservative treatment-policy estimand, which reflects participants who discontinued, it was up to 10.2% versus 1.4% for placebo.

The tolerability signal

Roche and Zealand have positioned petrelintide on tolerability rather than peak efficacy. In earlier topline reporting, the companies described no vomiting events and no gastrointestinal-related discontinuations at the maximally effective dose, with an overall adverse-event discontinuation rate of 4.8% against 4.9% for placebo. In the published analysis, nausea was more common on petrelintide than placebo — 20% versus 6% — and constipation was reported in 7% versus 4%. Rates of vomiting and diarrhoea were the same as, or lower than, placebo.

That profile is the class thesis. Amylin's first-generation member, pramlintide, was limited by nausea rates above 30% and three-times-daily injection. Whether petrelintide's tolerability advantage holds across a larger Phase 3 population is not yet established.

Where it sits in the amylin class

Amylin is co-secreted with insulin and signals satiety through the brainstem. Petrelintide is a selective amylin-receptor (AMYR) agonist with minimal calcitonin-receptor (CALCR) activity. Cagrilintide, the amylin component of CagriSema, is a dual AMYR/CALCR agonist. Eli Lilly's selective amylin agonist eloralintide reported up to 20.1% mean weight loss at 48 weeks in its Phase 2 study — a higher figure than petrelintide's, but across a different dose range, duration and population. Novo Nordisk's amycretin is a unimolecular GLP-1/amylin co-agonist rather than a pure amylin analogue. Cross-trial comparisons in this class are imprecise and should be read as directional only.

Roche is scheduled to begin three Phase 3 petrelintide studies — in obesity or overweight alone, with type 2 diabetes, and with cardiovascular disease — all testing monotherapy, with primary completion dates in late 2028.

The UK position

Petrelintide is not licensed in the UK and cannot lawfully be supplied as a medicine. Under the Medicines Act 1968 and the Human Medicines Regulations 2012, supplying an unlicensed product of this kind is a criminal offence, and the MHRA's Criminal Enforcement Unit has repeatedly acted against the manufacture and sale of unlicensed incretin and amylin products. Peptide Data covers these compounds for research and reference only; nothing here is guidance on human use, dosing or supply.

This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.