Petrelintide
Long-acting amylin analog
Also ZP8396, ZP-8396, Petrelintide injection
- Evidence
- BSome human evidence
- FDA status
- In clinical trialsas of 2026-10-27
- Route
- Injection
- Studies cited
- 2 human0 animal or cell
Sold for
Petrelintide is talked about as the amylin-based weight loss drug that might match GLP-1 injections for weight loss with far fewer stomach side effects.
Studies say
One published phase 2 trial shows about a tenth of body weight lost over 42 weeks with gastrointestinal tolerability close to placebo apart from mild nausea, which earns a B; the phase 3 program that would settle efficacy and safety is only starting.
Why grade B. One randomized, placebo-controlled phase 2 trial (ZUPREME-1, 485 adults with overweight or obesity, 42 weeks) has been published, and a second phase 2 trial in people with type 2 diabetes has reported topline results by press release. That is enough for B but not A: there is no phase 3 data yet and no long-term safety follow-up. 12
FDA. Petrelintide is an investigational drug in phase 3 development and is not approved by the FDA or any other regulator for any use. It is not legally available outside clinical trials. 12
Written from 2 cited sources. Fact-checked 2026-10-27: 16 claims checked, 1 corrected. Last refreshed 2026-10-27. Not physician reviewed.
Evidence checklist
- Randomised controlled trial ZUPREME-1 placebo-controlled phase 2yes
- Human study over 100 people 485 adults in ZUPREME-1yes
- More than one research group Sponsor-run trials, no replicationno
- Clinical outcomes, not surrogate markers Weight change, no outcomesno
- Human safety data beyond case reports 42 weeks, a few hundred peopleno
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Petrelintide is a long-acting synthetic analog of amylin, a hormone the pancreas releases alongside insulin after meals. It was designed by Zealand Pharma to be given as a once-weekly injection and is being developed with Roche. Unlike cagrilintide, the other long-acting amylin analog in late development, petrelintide is being tested on its own, not fixed in combination with a GLP-1 drug. 1
The phase 2 program is called ZUPREME. ZUPREME-1 enrolled adults with overweight or obesity and no diabetes; ZUPREME-2 enrolled adults who also have type 2 diabetes. A phase 3 program planned to enroll roughly 7,000 people was announced in 2026. 12
How it works
Amylin acts on receptors in the brainstem and hypothalamus that slow stomach emptying, blunt the rise in glucagon after a meal and increase the sense of fullness. Native amylin clumps into fibrils and has a half-life of minutes, which is why pramlintide, the first amylin drug, has to be injected at every meal. Petrelintide is modified to resist clumping and to bind to albumin in the blood, which stretches its action to about a week. The appetite effect runs through a different receptor system from GLP-1 drugs, which is the basis for the hope that it causes less nausea. 1
What human research shows
In ZUPREME-1, 485 adults with overweight or obesity and no diabetes received one of five petrelintide maintenance doses or placebo for 42 weeks at sites in Poland, Romania and the US. At 28 weeks, the primary endpoint, mean weight loss ranged from 7.9 to 9.8 percent across the dose groups against 1.7 percent on placebo, and it continued to a maximum of 10.7 percent by week 42. Nausea, mostly mild and during dose escalation, affected 20 percent of petrelintide participants versus 6 percent on placebo; vomiting, diarrhoea and constipation were no more common than on placebo. 1
ZUPREME-2, in 220 adults with overweight or obesity and type 2 diabetes, met its primary endpoint at 28 weeks with up to 9.2 percent weight loss against about 2 percent on placebo and a placebo-adjusted HbA1c fall of 0.61 to 0.88 points, according to the sponsor's October 2026 announcement. Full results have not been peer reviewed. 2
| Study | Model | Finding |
|---|---|---|
| ZUPREME-1 | Humans, n=485, randomized, double-blind, placebo-controlled, 42 weeks | Weight loss of 7.9 to 9.8 percent at 28 weeks versus 1.7 percent with placebo, reaching up to 10.7 percent by week 42; nausea more common than placebo, other gastrointestinal effects not. 1 |
| ZUPREME-2 topline | Humans, n=220 adults with type 2 diabetes and overweight or obesity, randomized double-blind placebo-controlled, three doses, 28 weeks | Met its primary endpoint with up to 9.2 percent weight loss; detailed data not yet published. 2 |
Safety
In the published trial the most common adverse event was nausea, mostly mild and concentrated in the dose-escalation period, at 20 percent versus 6 percent on placebo; vomiting, diarrhoea and constipation occurred at placebo-like rates and no deaths were reported. Trials of 42 weeks in a few hundred people cannot detect rare harms, and nothing is known about use beyond a year, about use in people with kidney or liver disease, or about pregnancy. Those gaps are what the phase 3 program is meant to fill. 12
Questions for your clinician
- Is petrelintide available only in trials?
- How does its nausea rate compare with GLP-1 drugs?
- What long-term safety data will phase 3 add?
Questions people ask
Is petrelintide FDA-approved?
No. It is in phase 3 trials and has not been submitted to the FDA. Anything sold online under that name is not a regulated product and its contents cannot be verified. 12
How does petrelintide differ from semaglutide and other GLP-1 drugs?
It works on the amylin receptor system instead of the GLP-1 receptor. Weight loss in phase 2 was somewhat below what semaglutide and tirzepatide produce, but nausea and vomiting were much less common, which is the trade-off its developers are betting on. 1
How does it compare with cagrilintide?
Both are weekly amylin analogs. Cagrilintide is mainly being developed in a fixed combination with semaglutide (CagriSema), while petrelintide is being tested alone first. There is no head-to-head trial. 1
Citations
- Garvey 2026, Lancet Diabetes Endocrinol: petrelintide for obesity (ZUPREME 1), randomised double-blind placebo-controlled phase 2 trial pubmed.ncbi.nlm.nih.gov
- HCPLive, Oct 2026: ZUPREME-2 topline results hcplive.com
Updates
- 2026-10-27 ZUPREME-1 citation switched from DOI to its PubMed record (PMID 42810355); corrected the weight-loss figures (7.9 to 9.8% at 28 weeks, up to 10.7% at 42) and the nausea rate (20% vs 6%), which the page had described as placebo-like.