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An amylin analogue engineered for chemical stability and a ~10-day half-life — the candidate behind the bet that amylin can match GLP-1 with fewer side effects.
Also known as: ZP8396 · ZP-8396
Part of the Metabolic & GLP-1 peptides cluster
Overview
Petrelintide (ZP8396) is an investigational long-acting analogue of human amylin developed by Zealand Pharma as a dual amylin and calcitonin receptor agonist. Its backbone replaces amylin's disulfide with an amide bridge and carries a C20 fatty diacid, giving a half-life of about 10 days; phase 1 dosing produced up to 8.6% weight loss at 16 weeks with mostly mild gastrointestinal effects. Phase 2 trials are under way as of September 2026.
Source & context
Biological / chemical source: Synthetic engineered human amylin analogue with a C20 fatty diacid on the N-terminus
Primary research or clinical context: Investigational (Zealand Pharma, partnered with Roche) — phase 2 in obesity and in overweight/obesity with type 2 diabetes
What petrelintide is
Petrelintide (ZP8396) is a long-acting, lipidated analogue of the anorexigenic peptide amylin, developed by Zealand Pharma for type 2 diabetes and obesity. Functionally it is a dual amylin and calcitonin receptor agonist (DACRA); such analogues are proposed to provide GLP-1-like efficacy with reduced propensity for side effects compared with glucagon and GLP-1 receptor agonists (IUPHAR ligand 13804). It is one of several long-acting amylin-based agents — with cagrilintide, eloralintide and NN1213 — that differ in pharmacokinetics and receptor selectivity (Fischer & Borner, Pharmacological Research 2026).
Structure: engineered for stability
The IUPHAR record lists an unusual set of modifications. The N-terminal glutamate carries a C20 fatty diacid through a γ-glutamate; an amide bridge between Asp3 and Lys8 replaces the disulfide that holds native amylin's N-terminal ring; position 15 is α-aminoadipic acid; Gly23 and Ile25 are N-methylated; and the chain ends in 4-hydroxyproline amide. The development paper describes optimisation of chemical stability while retaining in vitro and in vivo potency (Fischer Munch et al., Journal of Medicinal Chemistry 2025). The formula is C185H305N49O61 with a mass of about 4,192 Da (PubChem CID 172915807).
Phase 1: half-life and early weight loss
Two randomised, placebo-controlled phase 1 trials tested single subcutaneous doses of 0.04–2.4 mg (plus 0.35 mg intravenously) and multiple ascending once-weekly doses of 0.6 and 1.2 mg, then 16 weekly doses escalated every 2 weeks to 2.4, 4.8 and 9.0 mg in adults with overweight or obesity. Petrelintide was well tolerated with no serious or severe adverse events; gastrointestinal events were most common and mostly mild, with nausea in 16.7–33.3% versus 16.7% on placebo in the multiple-dose part, diarrhoea rare and vomiting in one participant who discontinued. It was slowly absorbed, had a half-life of about 10 days, showed dose-proportional steady state and reduced body weight by up to 8.6% after 16 weeks (Brændholt Olsen et al., Diabetes, Obesity and Metabolism 2026).
Phase 2 and partnership
ClinicalTrials.gov lists six studies as of September 2026: a completed phase 2 trial of once-weekly petrelintide in obesity or overweight with comorbidities (NCT06662539), an active phase 2 trial in overweight or obesity with type 2 diabetes (NCT06926842), pharmacokinetic studies in hepatic and renal impairment, and a planned Roche dose-finding study combining petrelintide with enicepatide (NCT07589686) — reflecting a partnership with Hoffmann-La Roche. Phase 2 efficacy results were not in the published literature reviewed for this profile.
Petrelintide vs cagrilintide vs eloralintide
All three are long-acting amylin analogues. Cagrilintide is the non-selective DACRA co-formulated with semaglutide as CagriSema; eloralintide is Lilly's AMY1R-selective agonist; petrelintide is Zealand's DACRA with the longest reported half-life of the three (about 10 days). A 2026 network meta-analysis compares amylin-based therapies on weight and gastrointestinal tolerability (Kamrul-Hasan et al., Endocrinology, Diabetes & Metabolism 2026), and a 2026 review surveys amylin analogues as the next major class of weight-loss therapy (Alhazmi et al., Diabetes, Obesity and Metabolism 2026). The cagrilintide and amylin profiles on this site cover the parent biology.
Status and what this page is not
Petrelintide is investigational and not approved anywhere as of September 2026. Vials sold online under the name are unlicensed material of unverified content; this profile is educational and not guidance on obtaining or using any product.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Human amylin analogue, 36 residues in the IUPHAR-deposited backbone, C-terminal amide
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
(C20 diacid-γGlu)-E-R-D-G-T-A-T-K-A-T-E-R-L-A-[Aad]-F-L-Q-R-S-S-F-G-A-I-L-S-S-T-E-V-G-S-N-T-[Hyp]-NH2, with an amide bridge Asp3–Lys8 replacing amylin's Cys2–Cys7 disulfide
- Molecular formula
- C185H305N49O61
- Average reference mass
- ≈ 4,192
- Plasma half-life
- ≈ 10 days (phase 1)
- Receptors
- Amylin receptors and the calcitonin receptor — a dual amylin/calcitonin receptor agonist (DACRA)
- Backbone
- Human amylin analogue, 36 residues in the IUPHAR-deposited backbone, C-terminal amide
- Lipidation
- Icosanedioic acid (C20 fatty diacid) via γ-glutamate on the N-terminal glutamate
- Status
- Investigational: phase 2 (obesity; overweight/obesity with type 2 diabetes); not approved as of September 2026
| Position | Native | Analog | Purpose |
|---|---|---|---|
| Glu1 | Lys1 (amylin) | Glu acylated with C20 diacid-γGlu | Albumin binding for once-weekly dosing |
| Asp3–Lys8 | Cys2–Cys7 disulfide | Amide (lactam) bridge | Chemical stability without a reducible disulfide |
| Position 15 | — | α-Aminoadipic acid | Stability and potency |
| Gly23, Ile25 | Gly, Ile | N-methyl-Gly, N-methyl-Ile | Backbone methylation to resist fibrillation and proteolysis |
| Position 36 | Tyr37 (amylin) | 4-Hydroxyproline amide | C-terminal stability |
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 9 registered studies with “Petrelintide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07843485 | A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesi | Phase 3 | not yet recruiting | 2026-09-28 |
| NCT07843498 | A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesi | Phase 3 | not yet recruiting | 2026-09-28 |
| NCT07843472 | A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesi | Phase 3 | not yet recruiting | 2026-09-28 |
| NCT06926842 | Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2) | Phase 2 | completed | 2026-09-09 |
| NCT07589686 | A Dose-Finding Study of Petrelintide With Enicepatide (RO7795068) in Adults With Obesity or Overweight | Phase 2 | not yet recruiting | 2026-09-09 |
| NCT07682818 | Pharmacokinetics of Petrelintide in Participants With Impaired Hepatic Function | Phase 1 | recruiting | 2026-07-06 |
Petrelintide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Human amylin analogue, 36 residues in the IUPHAR-deposited backbone, C-terminal amideAverage reference mass: 4,192 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- TrialsHighest registered trial phase moved from phase 2 to phase 3.
- Trials3 registered studies added on ClinicalTrials.gov (now 9).
- IdentifiersCross-linked to IUPHAR ligand 13804 and PubChem CID 172915807.
- TrialsClinicalTrials.gov snapshot added: 6 registered studies, highest phase 2.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Petrelintide
What is Petrelintide?+
Petrelintide (ZP8396) is an investigational long-acting analogue of human amylin developed by Zealand Pharma as a dual amylin and calcitonin receptor agonist. Its backbone replaces amylin's disulfide with an amide bridge and carries a C20 fatty diacid, giving a half-life of about 10 days; phase 1 dosing produced up to 8.6% weight loss at 16 weeks with mostly mild gastrointestinal effects. Phase 2 trials are under way as of September 2026.
What Canadian product status is recorded for Petrelintide?+
Canadian product status for Petrelintide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Petrelintide?+
Petrelintide is commonly described as approximately 36 amino acids (Long-acting lipidated amylin analogue (DACRA)).
What is petrelintide?+
ZP8396, an investigational long-acting amylin analogue from Zealand Pharma that activates amylin and calcitonin receptors. It is in phase 2 for obesity and type 2 diabetes.
How much weight loss did petrelintide produce?+
Up to 8.6% after 16 weeks in phase 1 multiple-dose cohorts; phase 2 results were not yet published in the literature reviewed here.
What is petrelintide's half-life?+
About 10 days in phase 1, supporting once-weekly injection.
Petrelintide vs cagrilintide — what is the difference?+
Both are DACRAs; cagrilintide is the CagriSema component and further along in development, while petrelintide was engineered for chemical stability with an amide bridge and a longer half-life.
Related peptides
References & further reading
- 1.Brændholt Olsen et al. (2026). Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Petrelintide for Weight Management: Two Randomized, Controlled Phase 1 Trials. Diabetes, Obesity and Metabolism
- 2.Fischer Munch et al. (2025). Development of Petrelintide: a Potent, Stable, Long-Acting Human Amylin Analogue. Journal of Medicinal Chemistry
- 3.Fischer & Borner (2026). Beyond GLP-1: Amylin-based pharmacotherapy and the search for better-tolerated weight-loss drugs. Pharmacological Research
- 4.Alhazmi et al. (2026). Amylin Analogs: The Next Major Class of Weight Loss Therapy. Diabetes, Obesity and Metabolism
- 5.Bailey et al. (2026). Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes. Peptides
- 6.PubChem — compound summary for Petrelintide (CID 172915807)