Petrelintide: Zealand Pharma's Long-Acting Amylin Analogue

Petrelintide (ZP8396) is a long-acting amylin analogue developed by Zealand Pharma for the treatment of obesity ^[1]. It is designed for once-weekly subcutaneous administration ^[2].

Mechanism

Petrelintide is an analogue of native human amylin engineered for chemical stability and a long duration of action, and it can be formulated at about neutral pH, which may allow co-formulation with other peptides ^[1]. In Phase 1 trials it had a half-life of about 10 days ^[2]. Like Eloralintide, it targets amylin receptors. The amylin class works principally by slowing gastric emptying, suppressing post-prandial glucagon, and acting on brain regions that regulate food intake ^[3,4].

Phase 2 Outcomes

In Phase 1, weight fell by up to 8.6% after 16 weeks ^[2]. In the ZUPREME 1 Phase 2 trial (493 adults with obesity, or overweight with hypertension or dyslipidaemia, without type 2 diabetes), mean weight reductions at 28 weeks ranged from 7.9% to 9.8% across doses versus 1.7% with placebo, and weight continued to fall to week 42 (up to 10.7%). Nausea was the most common side effect (20% vs 6% with placebo), mostly mild and during dose escalation, while other gastrointestinal effects were similar to placebo ^[5]. A Phase 2 study combining Petrelintide with Roche's enicepatide is registered but not yet recruiting (NCT07589686).

Position in the Amylin Class

• Cagrilintide (Novo Nordisk): dual amylin and calcitonin receptor agonist, furthest along in combination development (CagriSema, in Phase 3) ^[6].
• Eloralintide (Eli Lilly): selective amylin receptor agonist, combination data with Tirzepatide emerging.
• Petrelintide (Zealand): long-acting amylin analogue, with Phase 2 monotherapy data and Phase 3 trials registered.

Research Availability

See the Petrelintide research profile for receptor pharmacology, clinical-register status and citations, plus availability notifications. Petrelintide is not yet available as a research-grade peptide. The closest in-class compound available for amylin pathway research is Cagrilintide, with the Cagrilintide + Semaglutide blend available for combination work.

References

1. [1] Fischer Munch H, et al. "Development of Petrelintide: a Potent, Stable, Long-Acting Human Amylin Analogue." J Med Chem. 2025;68(22):23925-23940. PubMed 41217931
2. [2] Brændholt Olsen M, 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 42017294
3. [3] Hay DL, et al. "Amylin: Pharmacology, Physiology, and Clinical Potential." Pharmacol Rev. 2015;67(3):564-600. PubMed 26071095
4. [4] Dehestani B, et al. "Amylin as a Future Obesity Treatment." J Obes Metab Syndr. 2021;30(4):320-325. PubMed 34929674
5. [5] Garvey WT, 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. 2026 (online ahead of print). PubMed 42810355
6. [6] Garvey WT, et al. "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity." N Engl J Med. 2025;393(7):635-647. PubMed 40544433