Cagrilintide
Long-acting amylin analog designed to stack with semaglutide.
- Primary research area
- Weight / metabolic
- FDA status
- Phase 3 (Novo Nordisk) paired with semaglutide
- Last updated
- Apr 21, 2026
- Reviewed by
- Peptide Examiner editorial team
What it is
Cagrilintide is a long-acting amylin analog developed by Novo Nordisk. Amylin is a peptide hormone secreted by pancreatic beta cells alongside insulin; it slows gastric emptying and suppresses appetite via amylin and calcitonin receptors in the hindbrain — a pathway separate from GLP-1. Cagrilintide's primary commercial form is as CagriSema, a fixed-dose combination with semaglutide in a single injection, because the two mechanisms (amylin + GLP-1) produce additive weight loss.
Mechanism of action
Cagrilintide binds the amylin receptor (a complex of the calcitonin receptor with receptor activity-modifying proteins RAMP-1, -2, or -3) and calcitonin receptor in the area postrema and nucleus tractus solitarius, brainstem regions that regulate satiety and food intake. The result: reduced meal size, prolonged satiety, and slower gastric emptying — overlapping with GLP-1's effects but through different receptors, enabling additivity rather than competition when co-administered. Cagrilintide's engineering extends amylin's otherwise short half-life to allow weekly dosing.
Research history
Cagrilintide progressed through Phase 2 as monotherapy and in combination with semaglutide. The REDEFINE Phase 3 program tested CagriSema (cagrilintide + semaglutide). REDEFINE-1 (NEJM 2025) reported 20.4% mean weight loss at 68 weeks in adults with obesity — a substantial improvement over semaglutide alone (~15%) and competitive with tirzepatide (~21%) through a genuinely different mechanism. REDEFINE-2 extended to T2D populations.
Current trial status
Phase 3 complete. Novo Nordisk has submitted regulatory filings for CagriSema. FDA approval timeline uncertain; reasonable expectation is 2026-2027. Cagrilintide monotherapy is less commercially emphasized; the combination with semaglutide is the lead product.
Regulatory status
Investigational. Not FDA approved as of April 2026. Once approved, CagriSema will join the GLP-1-class market with a mechanistically differentiated combination. Full regulatory timeline →
Controversies and open questions
Whether the amylin-receptor addition is a net clinical win vs just using higher-dose semaglutide or switching to tirzepatide depends on readouts from future comparative trials. Tolerability of the combination has been broadly similar to semaglutide alone. The commercial question is whether a fixed-dose combination is worth it vs. the additional flexibility of separate-drug prescribing.
Further reading
Frequently asked
What's the main product — cagrilintide alone or CagriSema?
CagriSema — the fixed-dose combination with semaglutide. Novo Nordisk's lead commercial product. Cagrilintide monotherapy is less emphasized because the additive weight loss with GLP-1 co-administration is the distinctive clinical effect.
How is amylin different from GLP-1?
Amylin is a pancreatic hormone co-secreted with insulin. Its satiety pathway (via amylin/calcitonin receptors in the hindbrain) is separate from GLP-1's. Combining the two targets meal-size and satiety through complementary mechanisms rather than redundantly.
Is CagriSema approved yet?
Not as of April 2026. Novo has submitted regulatory filings. Expected FDA approval 2026-2027 depending on review.
How does it compare to retatrutide?
Roughly comparable mean weight loss in their respective Phase 3 trials (~20-24%). Different mechanisms (amylin + GLP-1 vs triple GIP/GLP-1/glucagon). CagriSema is ahead regulatorily; retatrutide is still in Phase 3.