Petrelintide
Zealand Pharma's amylin monotherapy — ZUPREME-1 Phase 2b hit its endpoints in March 2026 with up to 10.7% weight loss at 42 weeks and "placebo-like" GI tolerability. Roche-partnered since 2025; Phase 3 planned for late 2026.
A long-acting amylin analog developed by Zealand Pharma (and co-developed with Roche since a March 2025 exclusive licensing agreement) for once-weekly subcutaneous administration in chronic weight management, notable in the pipeline for its non-incretin mechanism and unusually favorable gastrointestinal tolerability relative to GLP-1-based therapies.
Mechanism of action
Mimics endogenous amylin — a peptide co-secreted with insulin from pancreatic beta cells in response to nutrient intake. Activates amylin receptors (calcitonin receptor + RAMP complexes) in the area postrema and related hindbrain circuits, reducing food intake by increasing satiety and, importantly, appearing to restore leptin sensitivity. The non-GLP-1 mechanism is the source of the markedly better GI tolerability profile observed in trials.
Primary uses
- Chronic weight management (Phase 2b completed, Phase 3 pending)
- Potential combination partner with GLP-1 agonists (e.g. Roche's CT-388, Phase 2 combination trial planned H1 2026)
Typical dosing
ZUPREME-1 tested five target doses up to 9 mg with dose escalation every four weeks.
Regulatory status
Not approved. Zealand Pharma developer, Roche co-development/co-commercialization partner (March 2025 agreement). ZUPREME-1 Phase 2b dose-finding trial (N=493) reported positive topline results March 5, 2026, with up to 10.7% mean body weight reduction at week 42 versus 1.7% for placebo, and no cases of vomiting and no treatment discontinuations from GI adverse events at the maximally effective dose. ZUPREME-2 (obesity/overweight with T2D) topline expected H2 2026. Phase 3 initiation planned for late 2026.
References
- [news-release] Zealand Pharma. "Zealand Pharma announces positive Phase 2 results for petrelintide." March 5, 2026.
- [news-release] Roche. "Roche announces positive Phase II results for petrelintide." March 5, 2026.
- [news-release] Roche. "Roche enters into an exclusive collaboration & licensing agreement with Zealand Pharma to co-develop and co-commercialise petrelintide." March 12, 2025.
Related peptides
This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.