Petrelintide vs Cagrilintide (2026): Amylin Analogue Trial Data Compared
Petrelintide reached 10.7% weight loss at 42 weeks; cagrilintide alone hit 11.8% at 68 weeks. See how the two once-weekly amylin analogues really compare.
Research reference only. The information in this article is a summary of peer-reviewed scientific literature. It does not constitute medical advice and is not intended to guide human use. See our full disclaimer.
Petrelintide vs cagrilintide is the comparison researchers make between two long-acting amylin analogues that have taken different development paths: Zealand Pharma and Roche's petrelintide, studied as a once-weekly monotherapy in the ZUPREME program (Phase 2 ZUPREME-1, NCT06662539), and Novo Nordisk's cagrilintide, studied mainly as the amylin half of the cagrilintide plus semaglutide combination known as CagriSema. Both act on amylin receptors, but their evidence bases, trial designs and regulatory positions differ enough that the headline numbers need careful reading.
Research reference only. All information on this page is a summary of peer-reviewed scientific literature and does not constitute medical advice. See individual library profiles for full compound data.
Quick Answer: As monotherapy, petrelintide produced up to 10.7% mean weight reduction at 42 weeks in Phase 2, while cagrilintide produced 10.8% at 26 weeks in its Phase 2 dose-finding trial and 11.8% at 68 weeks in the REDEFINE 1 monotherapy arm; cagrilintide's 20.4% figure comes from its combination with semaglutide, not from cagrilintide alone.
TL;DR:
- Both are once-weekly subcutaneous amylin analogues that act on calcitonin receptor/RAMP complexes rather than the GLP-1 receptor.
- Petrelintide (Zealand/Roche) is being developed primarily as a standalone agent and entered Phase 3a (ZUPREME-3, -4, -5) in September 2026.
- Cagrilintide (Novo Nordisk) is developed mainly inside CagriSema, which has a US regulatory submission filed in December 2025.
- Monotherapy figures for the two compounds sit in a similar range (about 10% to 12%), but the trials differ in length and design.
- Neither compound is FDA approved; both are investigational.
| Feature | Petrelintide | Cagrilintide |
|---|---|---|
| Developer | Zealand Pharma / Roche | Novo Nordisk |
| Most advanced stage | Phase 3a (monotherapy) | Phase 3 complete; combination filed |
| Monotherapy weight loss | Up to 10.7% at 42 weeks (Phase 2) | 10.8% at 26 weeks (Phase 2); 11.8% at 68 weeks (REDEFINE 1 arm) |
| Combination data | Enicepatide combination trial planned | 20.4% at 68 weeks with semaglutide (REDEFINE 1) |
| Dosing interval | Once weekly, subcutaneous | Once weekly, subcutaneous |
Petrelintide: mechanism and evidence base
Petrelintide (ZP8396, RG6849) is a long-acting human amylin analogue discovered by Zealand Pharma and co-developed with Roche under a 2025 collaboration. Its full profile is at /library/petrelintide/. The molecule was engineered to remain chemically and physically stable at neutral pH without forming fibrils, a known limitation of native amylin, which the developers describe as enabling co-formulation with other peptides.
Like other amylin analogues, petrelintide activates amylin receptors, which are heteromeric complexes of the calcitonin receptor and receptor activity-modifying proteins (RAMPs). Activation of these receptors is associated in the literature with earlier satiation, slower gastric emptying and suppression of postprandial glucagon.
The Phase 1 program is now PubMed-indexed. Two randomized, placebo-controlled trials reported in Diabetes, Obesity and Metabolism (PMID 42017294; NCT05096598, NCT05613387) found no serious or severe adverse events, mostly mild gastrointestinal events, a half-life of roughly 10 days and up to 8.6% body weight reduction after 16 weeks of once-weekly dosing.
The Phase 2 ZUPREME-1 trial (NCT06662539) randomized 493 adults with overweight or obesity without type 2 diabetes to one of five once-weekly doses or placebo. Mean weight reduction reached up to 10.7% at week 42 versus 1.7% with placebo under the efficacy estimand, and up to 10.2% versus 1.4% under the treatment-policy estimand. Waist circumference fell by up to 10.8 cm versus 4.3 cm, and hsCRP by up to 41% versus 6%. The sponsors reported no vomiting and no discontinuations for gastrointestinal events in the maximally effective arm. The full results were published in The Lancet Diabetes & Endocrinology in September 2026 and presented at EASD 2026; a PMID for that paper was not yet held in this library at the time of writing.
Cagrilintide: mechanism and evidence base
Cagrilintide is a long-acting synthetic amylin analogue developed by Novo Nordisk; its full profile is at /library/cagrilintide/. It binds amylin receptor subtypes AMY1R, AMY2R and AMY3R, engaging both hypothalamic (homeostatic) and mesolimbic (hedonic) satiety pathways. Fatty-acid acylation supports once-weekly administration, with a reported half-life of roughly 159 to 195 hours.
Cagrilintide's monotherapy evidence comes from a 26-week Phase 2 dose-finding trial published in The Lancet (PMID 34798060). In 706 adults with overweight or obesity without diabetes, doses from 0.3 mg to 4.5 mg produced dose-dependent weight reduction; the 4.5 mg dose reached 10.8% versus 3.0% with placebo, compared with 9.0% for the liraglutide 3.0 mg active control.
The compound's later-stage program has centered on combination with semaglutide. In the Phase 3 REDEFINE 1 trial (PMID 40544433), once-weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg produced 20.4% mean weight reduction at 68 weeks versus 3.0% with placebo. The trial also included single-agent arms, in which cagrilintide 2.4 mg alone produced 11.8% and semaglutide 2.4 mg alone 16.1%. That cagrilintide-alone arm is the closest long-duration reference point for comparison with petrelintide.
Side-by-side comparison
| Feature | Petrelintide | Cagrilintide |
|---|---|---|
| Receptor target | Amylin receptors (CTR/RAMP) | AMY1R, AMY2R, AMY3R |
| Reported half-life | About 10 days (Phase 1) | About 159–195 hours |
| Route and interval | Subcutaneous, once weekly | Subcutaneous, once weekly |
| Key monotherapy trial | ZUPREME-1, n=493, 42 weeks | Phase 2 dose-finding, n=706, 26 weeks |
| Maximum monotherapy weight loss | Up to 10.7% (placebo 1.7%) | 10.8% at 4.5 mg (placebo 3.0%) |
| Long-duration data | Phase 3a primary endpoint at week 64 (ongoing) | 11.8% at 68 weeks alone; 20.4% with semaglutide |
| Primary development strategy | Monotherapy first, combinations planned | Fixed combination with semaglutide |
| Regulatory status | Investigational | Investigational (combination under FDA review) |
Differential research applications
The two programs address different research questions. Petrelintide's program isolates the amylin pathway as a standalone mechanism, with tolerability placed at the center of the sponsors' framing. Its Phase 3a ZUPREME program, started September 22, 2026, includes ZUPREME-3 (about 3,900 participants without type 2 diabetes), ZUPREME-4 (about 600 with type 2 diabetes) and ZUPREME-5 (about 2,500 with established cardiovascular disease), each with percentage change in body weight at week 64 as the primary endpoint. A separate Phase 2 trial (NCT07589686) is planned to combine petrelintide with Roche's GLP-1/GIP agonist enicepatide.
Cagrilintide, by contrast, is the most studied reference for additive amylin plus GLP-1 signaling. Studies examining whether amylin receptor activation adds to GLP-1 receptor activation typically use the REDEFINE data set, because it includes combination and single-agent arms under one protocol. The cagrilintide vs semaglutide comparison covers those arms in more detail.
For researchers placing both compounds against the wider amylin field, eloralintide (Eli Lilly) and the unimolecular amylin/GLP-1 agonist amycretin are the other main reference points. The trial tracker lists registered studies for each compound by phase, and the half-life chart puts long-acting peptide pharmacokinetics in one view.
Reading the efficacy numbers carefully
The monotherapy figures look close, but they are not head-to-head evidence. Cagrilintide's 10.8% came from a 26-week trial, while petrelintide's 10.7% came from a 42-week trial, and the dose ranges, titration schedules and populations differ. The REDEFINE 1 monotherapy arm offers a longer 68-week reference, but it used a single 2.4 mg dose rather than a dose range. Comparisons between cagrilintide's 20.4% combination result and petrelintide's monotherapy data mix two different questions and should be avoided. No trial has compared the two compounds directly.
Regulatory and compounding status
Neither compound holds FDA or EMA approval. Novo Nordisk filed a New Drug Application for the cagrilintide plus semaglutide combination in December 2025, with a US decision described by the sponsor and trade press as expected in late 2026 or early 2027; that application covers the fixed combination rather than cagrilintide as a standalone product. Petrelintide entered registrational Phase 3a development in September 2026. Both are investigational peptides and are not eligible for 503A compounding. Neither appears by name on the WADA Prohibited List, though the list's S0 category covers pharmacological substances not approved for human therapeutic use. Sponsor timelines may change.
Cited studies
- PMID 42017294: "Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Petrelintide for Weight Management: Two Randomized, Controlled Phase 1 Trials" (Diabetes, Obesity and Metabolism, 2026). https://doi.org/10.1111/dom.70753
- PMID 34798060: "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial" (The Lancet, 2021). https://doi.org/10.1016/S0140-6736(21)01751-7
- PMID 40544433, "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)" (New England Journal of Medicine, 2025). https://doi.org/10.1056/NEJMoa2502081
- NCT06662539 (ZUPREME-1), ClinicalTrials.gov registry record for petrelintide Phase 2.
- Roche press release, March 5, 2026, ZUPREME-1 Phase 2 topline results: https://www.roche.com/media/releases/med-cor-2026-03-05
Frequently asked questions
Q: What is the difference between petrelintide and cagrilintide?
A: Both are once-weekly amylin analogues, but petrelintide is being developed by Zealand Pharma and Roche mainly as a standalone agent, while cagrilintide is developed by Novo Nordisk mainly in combination with semaglutide. Their monotherapy weight-loss figures fall in a similar range, but the trials differed in length and design.
Q: Is petrelintide better than cagrilintide?
A: No trial has compared them directly, so the published data cannot rank them. Petrelintide reported up to 10.7% weight reduction at 42 weeks, and cagrilintide reported 10.8% at 26 weeks and 11.8% at 68 weeks as monotherapy, under different protocols.
Q: Is cagrilintide the same as CagriSema?
A: No. Cagrilintide is the amylin analogue itself, while CagriSema is the fixed combination of cagrilintide 2.4 mg and semaglutide 2.4 mg. The 20.4% weight-loss figure from REDEFINE 1 refers to the combination.
Q: What phase is petrelintide in?
A: Petrelintide began Phase 3a trials (ZUPREME-3, ZUPREME-4 and ZUPREME-5) in September 2026, following the Phase 2 ZUPREME-1 trial (NCT06662539). A Phase 2 trial in people with type 2 diabetes, ZUPREME-2, is also part of the program.
Q: Are petrelintide or cagrilintide FDA approved?
A: Neither is FDA approved. A New Drug Application for the cagrilintide plus semaglutide combination was filed in December 2025, and petrelintide remains in Phase 3 development.
See also:
- Petrelintide vs eloralintide: amylin analogue Phase 2 data compared: the other new-generation pairing for petrelintide
- Eloralintide vs cagrilintide: how Lilly's selective amylin agonist compares with Novo's analogue
- Cagrilintide and CagriSema: amylin + GLP-1 Phase 3 research review: full REDEFINE program context
For laboratory research purposes only. Not for human or animal consumption. Compounds described are not approved by the FDA for human or veterinary use unless explicitly stated.