# Petrelintide > Zealand Pharma and Roche’s once-weekly amylin analog — positioned as a better-tolerated alternative to GLP-1. Phase 2 ZUPREME-1 reported up to 10.7% weight loss at 42 weeks. - Also known as: ZP8396 - Class: Metabolic - FDA approved: No - Canonical page: https://americanpeptide.com/catalog/petrelintide ## Overview Petrelintide is an investigational long-acting amylin analog designed for once-weekly dosing and — unlike native amylin — chemical and physical stability at neutral pH, which permits co-formulation with other peptides. Developed by Zealand Pharma and partnered with Roche in 2025, it is aimed at weight loss with fewer gastrointestinal side effects than the GLP-1 class. The Phase 2 ZUPREME-1 trial reported up to 10.7% mean weight reduction at 42 weeks versus 1.7% on placebo, with discontinuation for adverse events no higher than placebo. It is not approved. Amylin is the satiety hormone co-secreted with insulin. The native peptide is short-lived and aggregates into amyloid fibrils, which is why the first amylin drug, pramlintide, needs injections with every meal. Petrelintide is a second-generation answer: an acylated analog with a half-life of about ten days and no tendency to fibrillate at neutral pH — the property that lets it be mixed in one solution with a GLP-1 or GIP/GLP-1 agonist. Zealand Pharma’s thesis is tolerability. If amylin agonism can deliver meaningful weight loss with less nausea and vomiting than the incretins, it has a role both as a standalone option for people who cannot stay on GLP-1 therapy and as a combination partner. In March 2025 Roche entered a co-development and co-commercialization agreement for the molecule, including combination with its own GIP/GLP-1 agonist CT-388. The Phase 2 ZUPREME-1 trial, reported in 2026, enrolled about 490 adults with obesity or overweight and met its primary endpoint at week 28; at week 42 mean weight reduction reached 10.7% on the top dose versus 1.7% on placebo. Nausea was reported by 19.6% of participants on petrelintide versus 6.2% on placebo, and discontinuation for adverse events was 4.8% versus 4.9%. The weight effect is smaller than the leading incretins — or than Lilly’s amylin agonist eloralintide in its own Phase 2 — so the program’s case rests on the tolerability profile. Phase 3 monotherapy trials were slated to start in the second half of 2026. ## Mechanism Agonism at amylin and calcitonin receptors → hindbrain satiety signaling and slowed gastric emptying. A pathway distinct from GLP-1, studied for restoring leptin sensitivity and reducing food intake through increased fullness rather than nausea. ## Chemistry | Property | Value | | --- | --- | | Molecular formula | C185H305N49O61 | | Molecular weight | 4192 Da | | PubChem CID | [172915807](https://pubchem.ncbi.nlm.nih.gov/compound/172915807) | ## Research areas Studied in: Obesity, Type 2 diabetes, Amylin pathway, Combination metabolic therapy. Guides on this site: - [Weight Loss & Metabolic Health](https://americanpeptide.com/research-areas/weight-loss): Incretin and metabolic peptides studied for glycemic control and fat loss. ## Key research - Long-acting amylin analog — once-weekly, ~10-day half-life, engineered against the fibril formation of native amylin. - Neutral-pH stability — allows co-formulation with GLP-1-class peptides in a single solution. - ZUPREME-1 (Phase 2, 2026) — up to 10.7% mean weight reduction at 42 weeks versus 1.7% placebo. - Tolerability — nausea 19.6% versus 6.2% placebo; discontinuation for adverse events 4.8% versus 4.9%. - Status — partnered with Roche (2025); Phase 3 program slated to begin in the second half of 2026; investigational. ## FAQs ### What is petrelintide? Petrelintide (ZP8396) is an investigational once-weekly amylin analog from Zealand Pharma, co-developed with Roche, studied for weight management as a monotherapy and in combination with incretin agonists. ### How is petrelintide different from GLP-1 drugs? It works through amylin and calcitonin receptors rather than the GLP-1 receptor. The weight loss reported so far is smaller than semaglutide or tirzepatide, but Phase 2 discontinuation for adverse events matched placebo — tolerability is the intended advantage. ### How does it compare with cagrilintide and eloralintide? All three are long-acting amylin-pathway agonists. Cagrilintide (Novo Nordisk) is the amylin half of CagriSema; eloralintide (Eli Lilly) reported larger Phase 2 weight loss; petrelintide (Zealand/Roche) emphasizes tolerability and co-formulation. They have not been compared head-to-head. ### How much weight do people lose on petrelintide? In the Phase 2 ZUPREME-1 trial, up to 10.7% mean weight reduction at 42 weeks versus 1.7% on placebo. Population means from a Phase 2 trial, not individual predictions. ### Is petrelintide approved? No — it is investigational and has not completed Phase 3. This page is a research reference, not medical advice. ## Latest research Recent trials and publications mentioning Petrelintide, pulled automatically from ClinicalTrials.gov and PubMed (unfiltered search results, refreshed daily). ### Recent trials - [A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes](https://clinicaltrials.gov/study/NCT07843485) — RECRUITING · PHASE3 · NCT07843485 - [A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity](https://clinicaltrials.gov/study/NCT07843498) — RECRUITING · PHASE3 · NCT07843498 - [A Dose-Finding Study of Petrelintide With Enicepatide (RO7795068) in Adults With Obesity or Overweight](https://clinicaltrials.gov/study/NCT07589686) — NOT_YET_RECRUITING · PHASE2 · NCT07589686 - [A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Established Cardiovascular Disease](https://clinicaltrials.gov/study/NCT07843472) — RECRUITING · PHASE3 · NCT07843472 - [Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2)](https://clinicaltrials.gov/study/NCT06926842) — COMPLETED · PHASE2 · NCT06926842 - [Pharmacokinetics of Petrelintide in Participants With Impaired Hepatic Function](https://clinicaltrials.gov/study/NCT07682818) — RECRUITING · PHASE1 · NCT07682818 --- Source: AmericanPeptide.com — https://americanpeptide.com/catalog/petrelintide Data license: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Attribution: AmericanPeptide.com. Research reference only — computational and educational content, not medical advice.