Petrelintide, a weekly amylin injection from Zealand Pharma and Roche, produced up to 10.7% average weight loss at 42 weeks in its main phase 2 trial, with vomiting in 3% of people against 6% on placebo. ZUPREME 1 was published in The Lancet Diabetes & Endocrinology on 29 September 2026 and presented at EASD 2026 in Milan on 30 September. A second trial in type 2 diabetes, ZUPREME-2, followed on 7 October.
What happened
ZUPREME 1 (PubMed 42810355) gave 485 adults with obesity, or overweight with high blood pressure or cholesterol, and without diabetes, one of five weekly doses of petrelintide (1.0 mg to 9.0 mg) or placebo for 42 weeks. Average starting weight was 107.1 kg. The trial ran at 32 sites in Poland, Romania and the US and was funded by Zealand.
| Dose | Weight lost at 28 weeks |
|---|---|
| Placebo | 1.7% |
| 1.0 mg | 7.9% |
| 2.5 mg | 7.9% |
| 5.0 mg | 9.8% |
| 7.0 mg | 9.3% |
| 9.0 mg | 9.4% |
Weight was still falling at week 42, when the best result reached 10.7%. These figures use the efficacy estimand, which assumes people stayed on treatment.
The side effects are the reason this drug is being watched:
| Side effect | Petrelintide | Placebo |
|---|---|---|
| Nausea | 20% | 6% |
| Vomiting | 3% | 6% |
| Diarrhoea | 7% | 7% |
| Constipation | 7% | 4% |
No deaths were reported. The lead author, Dr W. Timothy Garvey of the University of Alabama at Birmingham, told Healio: "That's about half the rate of nausea that we see in GLP-1 trials."
ZUPREME-2, announced by Zealand on 7 October 2026, tested three doses in 220 people with overweight or obesity and type 2 diabetes for 28 weeks. Weight fell 7.4% to 9.2% against 2.0% on placebo, and A1C fell by up to 0.65 points while it rose 0.23 on placebo. Stopping because of gut side effects was 1.9% on petrelintide and 1.7% on placebo. These are topline results from a company release and have not yet been published.
What it does not tell us
- How it compares head to head. Neither trial included a GLP-1, so the comparison with semaglutide or tirzepatide is across different trials, with different people.
- Whether more weight loss is possible. The doses above 5 mg did not add much at 28 weeks. Zealand has said a phase 2 trial combining petrelintide with another of its drugs, enicepatide, is planned for the second half of 2026.
- What happens beyond 42 weeks, or how much of the loss is muscle.
What it means for you
About 10% is a smaller loss than the GLP-1 and combination drugs presented at EASD this year, though the trials and the people in them differ. The case for petrelintide is tolerability: it could suit people who cannot stay on a GLP-1 because of nausea and vomiting, or who need to lose less. If that is you, it is worth knowing it exists, but it is years from a pharmacy. As of October 2026 Zealand has started phase 3, ZUPREME-3, 4 and 5, with about 7,000 people.
If the nausea on your current GLP-1 is the problem now, nausea on day 3 has practical steps, staying on a GLP-1 covers what helps people keep going, and your prescriber can talk you through dose options.
What to do with this
Any drug that makes you feel full sooner shrinks how much you eat at each meal. Put protein first on the plate so the smaller meal still covers what your muscles need.