Overview
Petrelintide is an investigational once-weekly amylin analog peptide originally developed by Zealand Pharma and partnered with Roche/Genentech in 2024. Amylin is a natural pancreatic peptide co-secreted with insulin that contributes to satiety, slows gastric emptying, and regulates postprandial glucose. Petrelintide is engineered as a long-acting amylin receptor agonist designed for sustained weekly dosing, with the goal of achieving meaningful weight loss with better gastrointestinal tolerability than GLP-1 receptor agonists. Late-breaking Phase 2 ZUPREME-1 data presented at ADA 2026 in June showed clinically meaningful weight loss with what Roche has described as a 'compelling tolerability profile.' The strategic interest in petrelintide centers on its potential combination with enicepatide (CT-388): pairing an amylin agonist with a dual GLP-1/GIP agonist could deliver additive weight loss while distributing GI side effects across mechanisms. A Phase 2 fixed-dose combination study with enicepatide is targeted to enroll its first patient around mid-2026.
Mechanism of Action
Petrelintide is a long-acting amylin analog that activates amylin receptors (AMY1, AMY2, AMY3 receptor complexes formed by the calcitonin receptor in association with receptor activity-modifying proteins). Activation reduces food intake, slows gastric emptying, and suppresses postprandial glucagon secretion. The molecule is designed for once-weekly subcutaneous dosing.
Potential Benefits
- Once-weekly amylin agonist for weight management
- Tolerability profile distinct from GLP-1-only agonists (less GI burden in early data)
- Combination potential with GLP-1/GIP agonists like enicepatide
Research Dosage Notes
The following reflects doses used in published research studies. This is not medical advice.
Once-weekly subcutaneous; dose regimens under Phase 2 evaluation.
Amino Acid Sequence
Proprietary long-acting amylin analog
Side Effects & Safety
- Mostly mild-to-moderate GI in early data
- Long-term safety still under evaluation
Synergistic Compounds
The following compounds have been studied alongside Petrelintide for potential complementary or synergistic effects:
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References & Further Reading
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