Petrelintide (research code ZP8396) is an investigational, long-acting analogue of amylin, a hormone the pancreas releases together with insulin after meals. Zealand Pharma developed it, and since 2025 it has been co-developed with Roche as a once-weekly injection for chronic weight management (Roche, 2025).
The single most important fact: petrelintide is not approved anywhere. As of October 2026 it has completed two phase 2 trials, and a phase 3 program of three placebo-controlled trials (ZUPREME-3, -4 and -5, about 7,000 participants planned) has begun dosing participants (Zealand Pharma, October 2026). All published human data come from trials funded by the developer.
This page summarizes what the clinical trials, trial registries and company disclosures report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Long-acting human amylin analogue; agonist at amylin and calcitonin receptors |
| Developer | Zealand Pharma (code ZP8396), co-developed with Roche since 2025 |
| Route | Subcutaneous injection, once weekly |
| Doses studied | Single doses 0.04–2.4 mg in phase 1; weekly maintenance doses 1.0–9.0 mg in phase 2 |
| Half-life | ≈ 10 days (mean 213–257 h after single subcutaneous doses) in phase 1 |
| Key design feature | Stable at neutral pH without forming fibrils, so it can be mixed with other peptide drugs |
| Development stage | Phase 3 started in 2026; phase 2 results published or announced |
| US status | Not FDA-approved; investigational drug only |
| WADA status | Not named on the 2026 List; as an unapproved drug it falls under S0 (non-approved substances), prohibited at all times |
What it is
Amylin is a 37-amino-acid peptide hormone made in the pancreatic beta cells. It acts mainly in the hindbrain to promote fullness, slow stomach emptying and suppress glucagon after meals (Fischer Munch et al., J Med Chem 2025). Native amylin makes a poor drug: it lasts only briefly in the body, breaks down chemically in solution and tends to clump into amyloid fibrils. The first amylin drug, pramlintide, was approved by the FDA in 2005 for people with diabetes who use insulin, but it needs several injections a day and must be formulated at acidic pH (Fischer Munch et al., 2025).
Zealand’s chemists started from human amylin and set out to make a version that is long-acting and stable at neutral pH. The published design paper describes these changes (Fischer Munch et al., 2025):
| Problem with native amylin | How petrelintide addresses it |
|---|---|
| Forms amyloid fibrils | Two backbone N-methyl groups in the fibril-forming region, instead of the proline substitutions used in pramlintide |
| Chemical breakdown in solution (deamidation) | Asparagine residues prone to degradation were replaced or deleted |
| Fragile disulfide bridge near the N-terminus | Replaced by a more stable lactam (amide) bridge |
| Very short half-life | A fatty acid side chain lets it bind reversibly to albumin in the blood, slowing clearance |
The albumin-binding description comes from the phase 1 report (Brændholt Olsen et al., Diabetes Obes Metab 2026). That report describes petrelintide as a 37-amino-acid acylated peptide of 4.2 kDa. PubChem lists the formula C₁₈₅H₃₀₅N₄₉O₆₁ and a molecular weight of about 4,192 g/mol (PubChem). In laboratory testing, it showed no fibrillation or substantial clumping after up to one month at 40 °C in common neutral-pH buffers, which is what allows it to be co-formulated with other peptides such as GLP-1 drugs (Fischer Munch et al., 2025).
Mechanism
Amylin receptors are the calcitonin receptor paired with one of three receptor activity-modifying proteins (RAMPs), giving the AMY1, AMY2 and AMY3 receptors. In cell assays, petrelintide activated the AMY3 receptor with potency similar to human amylin and also activated the calcitonin receptor (Fischer Munch et al., 2025). The phase 1 authors describe it as a potent agonist at AMY1, AMY3 and the calcitonin receptor (Brændholt Olsen et al., 2026). The same authors group it with cagrilintide and eloralintide as long-acting amylin analogues in clinical development.
Zealand and Roche describe amylin receptor activation as restoring sensitivity to the satiety hormone leptin, so people feel full sooner (Roche, 2025). This works through a different receptor system from GLP-1 drugs such as semaglutide and tirzepatide.
In rats, a single dose had a circulating half-life of 33.8 h and reduced body weight by about 10% at 96 h, and it lowered food intake and body weight in a dose-dependent way in diet-induced obese rats (Fischer Munch et al., 2025). These are animal findings.
Pharmacokinetics
Human pharmacokinetic data come from two phase 1 trials at one German center: a single ascending dose trial (subcutaneous 0.04–2.4 mg, plus one 0.35 mg intravenous cohort) and a multiple ascending dose trial with weekly dosing up to 9.0 mg (Brændholt Olsen et al., 2026).
| Parameter | Finding |
|---|---|
| Absorption | Slow; median time to peak 28–108 h after a single subcutaneous dose, earlier at higher doses |
| Bioavailability | 77.4% for a 0.35 mg subcutaneous dose |
| Half-life (subcutaneous) | ≈ 10 days (mean 213–257 h across cohorts) |
| Half-life (intravenous) | 239 h, so route did not change elimination |
| Steady state | Reached after the fifth weekly dose |
| Dose proportionality | Exposure (AUC and peak level) rose in proportion to dose from 0.6 to 9.0 mg at steady state |
| Anti-drug antibodies | None detected in either trial |
The long half-life supports once-weekly dosing. Dedicated studies of petrelintide in people with kidney impairment (completed) and liver impairment (recruiting) are registered, but their results have not been published (NCT07076030; NCT07682818).
Development and regulatory status
- Not approved. No regulator has approved petrelintide for any use. It is available only inside clinical trials.
- Roche partnership. In March 2025 Roche and Zealand agreed to co-develop and co-commercialize petrelintide, both as a stand-alone drug and as a fixed-dose combination with Roche’s GLP-1/GIP dual agonist CT-388 (now named enicepatide) (Roche, 2025; Zealand Pharma, 2026).
- Phase 2 complete. ZUPREME-1 (obesity without diabetes) was published in September 2026, and topline results from ZUPREME-2 (obesity with type 2 diabetes) were announced on October 7, 2026.
- Phase 3 under way. Zealand reported on October 7, 2026 that the phase 3a program had started and the first participants had begun treatment (Zealand Pharma, 2026). Roche is listed as the sponsor of all three trials on ClinicalTrials.gov:
| Trial | Population | Planned n | Primary endpoint | Estimated primary completion |
|---|---|---|---|---|
| ZUPREME-3 (NCT07843498) | Overweight or obesity with at least one weight-related condition, no type 2 diabetes | 3,900 | Body weight change at week 64 | December 2028 |
| ZUPREME-4 (NCT07843485) | Overweight or obesity with type 2 diabetes | 600 | Body weight change at week 64 | October 2028 |
| ZUPREME-5 (NCT07843472) | Overweight or obesity with established cardiovascular disease | 2,500 | Body weight change at week 64 | July 2030 |
A separate phase 2 dose-finding trial, ZYNERGY, will test petrelintide given together with enicepatide against each drug alone and placebo over 40 weeks in 486 planned participants; it was listed as not yet recruiting at its last registry update (NCT07589686).
What the research shows
Phase 1: first weekly-dosing data
In part 2 of the multiple ascending dose trial, 48 adults with overweight or obesity (mean BMI 29.9) received petrelintide or placebo once weekly for 16 weeks, with doses escalated every 2 weeks and no lifestyle program (Brændholt Olsen et al., 2026):
| Cohort (n=12 each) | Weeks at target dose | Observed weight change at week 16 | Waist change |
|---|---|---|---|
| Placebo | — | −1.7% | −1.9 cm |
| Target 2.4 mg | 12 | −4.8% | −5.0 cm |
| Target 4.8 mg | 8 | −8.6% | −7.2 cm |
| Target 9.0 mg | 6 | −8.3% | −7.6 cm |
Estimated differences from placebo were −3.2, −7.0 and −6.7 percentage points (p ≤ 0.0002 for all). The cohorts were small and about 80% male, and HbA1c (average blood sugar over about three months) did not change in these participants without diabetes.
Obesity without diabetes (ZUPREME-1)
ZUPREME-1 was a randomized, double-blind, placebo-controlled phase 2 trial at 32 sites in Poland, Romania and the USA (Garvey et al., Lancet Diabetes Endocrinol 2026; NCT06662539). It included 485 dosed adults without type 2 diabetes who had a BMI of at least 30, or at least 27 with high blood pressure or abnormal lipids (mean weight 107.1 kg, mean BMI 36.7). They were randomized 5:1 to one of five weekly petrelintide maintenance doses or placebo for 42 weeks including dose escalation.
| Arm | n | Weight change at week 28 (95% CI) | Difference vs placebo (95% CI) |
|---|---|---|---|
| Placebo | 81 | −1.7% (−2.8 to −0.5) | — |
| Petrelintide 1.0 mg | 79 | −7.9% (−9.0 to −6.7) | −6.2 (−7.9 to −4.5) |
| Petrelintide 2.5 mg | 81 | −7.9% (−9.0 to −6.7) | −6.2 (−7.8 to −4.5) |
| Petrelintide 5.0 mg | 83 | −9.8% (−10.9 to −8.6) | −8.1 (−9.7 to −6.5) |
| Petrelintide 7.0 mg | 79 | −9.3% (−10.5 to −8.2) | −7.7 (−9.3 to −6.0) |
| Petrelintide 9.0 mg | 82 | −9.4% (−10.5 to −8.3) | −7.7 (−9.4 to −6.1) |
These figures use the efficacy estimand, which assumes participants stayed on treatment. Key points:
- Plateau above 5 mg. Weight loss at week 28 was similar for the 5.0, 7.0 and 9.0 mg doses.
- Still falling at week 42. Weight continued to decline to the end of treatment, reaching up to −10.7%.
- Context. The phase 1 authors note that semaglutide and tirzepatide produce sustained weight loss of up to 15% or more (Brændholt Olsen et al., 2026). Trials differ in length, population and design, so direct comparison with ZUPREME-1 is not reliable.
Obesity with type 2 diabetes (ZUPREME-2)
ZUPREME-2 randomized 220 US adults with overweight or obesity and type 2 diabetes, taking metformin with or without an SGLT2 inhibitor, to one of three weekly petrelintide doses or placebo for 28 weeks, with doses escalated every fourth week (NCT06926842). Mean baseline BMI was 36.3 and mean HbA1c 8.0%. Only topline results from a company announcement are available, and the doses tested have not been disclosed (Zealand Pharma, 2026):
| Outcome at week 28 | Petrelintide (3 arms) | Placebo |
|---|---|---|
| Mean weight change (efficacy estimand) | −7.4% to −9.2% | −2.0% |
| HbA1c change | Down by up to 0.65 points | Up 0.23 points |
| Placebo-adjusted HbA1c change | −0.61 to −0.88 points | — |
| Stopped treatment because of GI side effects | 1.9% | 1.7% |
All three doses met the primary endpoint. Full results have not yet been peer-reviewed.
What is still unknown
- Long-term effects. The longest published treatment period is 42 weeks. Phase 3 trials run to week 64, with primary completion estimated from late 2028.
- Body composition. Rat data presented at a 2024 conference suggested fat loss with lean mass preserved (cited in Brændholt Olsen et al., 2026). ZUPREME-1 included an MRI subgroup, but body-composition results are not reported in the published abstract. There are no published human data showing that petrelintide spares muscle.
- Cardiovascular outcomes. ZUPREME-5 includes people with heart disease, but its primary endpoint is weight change, not heart attacks or strokes.
- Combination therapy. No human results for petrelintide combined with enicepatide or any GLP-1 drug have been published.
Side effects and risks
Gastrointestinal effects
Nausea is the main side effect, as with other amylin and GLP-1 drugs, and it occurs mostly during dose escalation. In ZUPREME-1, the reported rates were (Garvey et al., 2026):
| Adverse event | Petrelintide (n=404) | Placebo (n=81) |
|---|---|---|
| Nausea | 20% | 6% |
| Vomiting | 3% | 6% |
| Diarrhea | 7% | 7% |
| Constipation | 7% | 4% |
The authors described the nausea as predominantly mild, and no deaths were reported. In the phase 1 weekly-dosing trial, nausea affected 17–33% of people on petrelintide vs 17% on placebo, and one of 36 participants stopped because of moderate nausea and vomiting (Brændholt Olsen et al., 2026). In ZUPREME-2, discontinuation due to gastrointestinal events was 1.9% vs 1.7% with placebo (Zealand Pharma, 2026).
These low rates come from developer-funded trials of modest size. Rare side effects cannot be detected until the much larger phase 3 trials report.
Other findings in early trials
From the phase 1 trials (Brændholt Olsen et al., 2026):
- Appetite. Decreased appetite was reported in 58–83% of participants per petrelintide cohort vs 42% on placebo, consistent with how the drug works.
- Heart rate. Mean pulse fell by about 5 beats per minute by the end of weekly treatment.
- Injection sites. Reactions were mild and transient, mostly in participants who needed up to three injections per dose.
- No serious or severe adverse events and no clinically significant laboratory, ECG or vital-sign findings in either trial.
Hypoglycemia and diabetes medicines
Amylin slows stomach emptying and suppresses glucagon after meals (Fischer Munch et al., 2025), so effects on blood sugar matter for people taking diabetes medicines. No hypoglycemia (low blood sugar) data for petrelintide have been published beyond the ZUPREME-2 topline statement that there were no unexpected safety signals, and ZUPREME-2 participants were on metformin with or without an SGLT2 inhibitor, not insulin (Zealand Pharma, 2026).
Unregulated products
Because petrelintide is investigational, any product sold outside a clinical trial comes from outside the regulated drug supply. Its identity, purity, dose and sterility are not verified by any regulator, and such products have never been studied in people.
Legal status and use in sport
Petrelintide is not named on the WADA Prohibited List. However, the S0 class bans any pharmacological substance not covered elsewhere on the List that has no current approval by any government health authority, explicitly including drugs “under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an unapproved investigational drug, petrelintide falls into that class and is prohibited at all times. Its status could change if a regulator approves it.
Key takeaways
- A once-weekly amylin analogue. Petrelintide is a modified, lipidated version of human amylin with a half-life of about 10 days, designed to stay stable at neutral pH so it can be combined with other peptides.
- Not an approved drug. As of October 2026, petrelintide is in phase 3 trials run by Roche and Zealand Pharma; it is not approved anywhere.
- About 8–11% weight loss in phase 2. In ZUPREME-1, weekly doses produced 7.9–9.8% weight loss at 28 weeks and up to 10.7% at 42 weeks, vs 1.7% with placebo; ZUPREME-2 reported 7.4–9.2% in people with type 2 diabetes.
- Nausea is the main side effect. Nausea affected 20% vs 6% with placebo in ZUPREME-1, while vomiting and diarrhea were no more common than with placebo.
- Muscle-sparing claims are unproven. The only lean-mass data are from rats; human body-composition results have not been published.
- Prohibited in sport. As an unapproved drug it falls under WADA’s S0 class.
Sources
- Fischer Munch H, Just R, Mosolff Mathiesen J, et al. Development of Petrelintide: a Potent, Stable, Long-Acting Human Amylin Analogue. J Med Chem. 2025;68(22):23925–23940. PubMed.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 172915807, Petrelintide. PubChem.
- Brændholt Olsen M, Griffin J, Hövelmann U, et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Petrelintide for Weight Management: Two Randomized, Controlled Phase 1 Trials. Diabetes Obes Metab. 2026;28(7):5915–5925. PubMed.
- Garvey WT, Ard J, Connery L, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. Published online September 29, 2026. doi:10.1016/S2213-8587(26)00213-5. PubMed.
- Zealand Pharma. Zealand Pharma announces positive Phase 2 ZUPREME-2 topline results for amylin analog petrelintide in people with overweight or obesity and type 2 diabetes. Company announcement No. 54/2026, October 7, 2026. Nasdaq.
- Roche. Roche enters into an exclusive collaboration & licensing agreement with Zealand Pharma to co-develop and co-commercialise petrelintide as a potential foundational therapy for people with overweight and obesity. Press release, March 12, 2025. Roche.
- ClinicalTrials.gov. Once-weekly Petrelintide Versus Placebo for Obesity or Overweight With Co-morbidities (ZUPREME). NCT06662539. ClinicalTrials.gov.
- ClinicalTrials.gov. Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2). NCT06926842. ClinicalTrials.gov.
- ClinicalTrials.gov. A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity (ZUPREME-3). NCT07843498. ClinicalTrials.gov.
- ClinicalTrials.gov. A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME-4). NCT07843485. ClinicalTrials.gov.
- ClinicalTrials.gov. A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Established Cardiovascular Disease (ZUPREME-5). NCT07843472. ClinicalTrials.gov.
- ClinicalTrials.gov. A Dose-Finding Study of Petrelintide With Enicepatide (RO7795068) in Adults With Obesity or Overweight (ZYNERGY). NCT07589686. ClinicalTrials.gov.
- ClinicalTrials.gov. Pharmacokinetics of Petrelintide Following Administration to Participants With Impaired Renal Function. NCT07076030. ClinicalTrials.gov.
- ClinicalTrials.gov. Pharmacokinetics of Petrelintide in Participants With Impaired Hepatic Function. NCT07682818. ClinicalTrials.gov.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.