Petrelintide

Amylin works as a natural satiety signal: it is released after eating and helps end a meal¹. It acts on amylin receptors, which are complexes built around the calcitonin receptor, and much of its effect on appetite comes from the brain². Human amylin tends to clump, so the first amylin drug, pramlintide, was modelled on the non-clumping rat form². Petrelintide was engineered from human amylin to stay chemically stable in solution near neutral pH while keeping its potency, and to last much longer in the body. The developers also designed it so it could potentially be combined with other weight-management peptides¹. In early human studies it was absorbed slowly and had a half-life of about ten days³.

The human data come from developer-run trials. Two phase 1 studies in adults with normal weight, overweight or obesity found mostly mild gastrointestinal side effects and weight loss of up to 8.6% after 16 weeks³. In the phase 2 ZUPREME 1 trial, funded by Zealand, 485 adults with obesity, or overweight plus high blood pressure or abnormal blood lipids, and without type 2 diabetes received one of five dose levels or placebo⁴. After 28 weeks, mean body-weight change ranged from -7.9% to -9.8% on petrelintide versus -1.7% on placebo, and weight kept falling to week 42, reaching up to -10.7%⁴.

A second phase 2 trial, ZUPREME 2, in 221 people with overweight or obesity and type 2 diabetes finished in August 2026; we found no published results as of October 2026⁶. Roche-sponsored phase 3 trials are recruiting, including one in people with established cardiovascular disease⁵. Long-term outcomes are unknown.

Petrelintide is not approved by the FDA, and we found no approval by any other regulator; it is an investigational drug in phase 3 trials⁵.

Human data come only from trials. In ZUPREME 1, nausea was the most common adverse event (20% on petrelintide vs 6% on placebo). It was mostly mild and occurred mainly while the dose was being increased. Vomiting, diarrhea and constipation were infrequent and close to placebo rates, and no deaths were reported⁴. The phase 1 studies reported mainly mild gastrointestinal effects, and one participant stopped because of them³. Effects beyond about ten months of use have not been reported.

1. Fischer Munch et al., J Med Chem 2025PubMed
2. Bailey et al., Peptides 2026PubMed
3. Brændholt Olsen et al., Diabetes Obes Metab 2026PubMed
4. Garvey et al., Lancet Diabetes Endocrinol 2026PubMed
5. ClinicalTrials.gov: NCT07843472ClinicalTrials.gov
6. ClinicalTrials.gov: NCT06926842ClinicalTrials.gov