Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
Cagrilintide — internal code AM833 — is a synthetic, long-acting analog of amylin, the peptide hormone co-secreted with insulin by pancreatic beta cells. Native amylin has a half-life of only 13 minutes and is too unstable for therapeutic use; pramlintide (Symlin), the only approved amylin analog, requires three to four daily injections. Novo Nordisk redesigned the backbone and added a C18 fatty acid side chain to extend cagrilintide's half-life to roughly 6 to 7 days, enabling once-weekly subcutaneous dosing.
The compound is being developed primarily as part of CagriSema, a fixed-ratio combination of cagrilintide and semaglutide.
History
Novo Nordisk published cagrilintide's chemistry in 2021 (Kruse et al., J Med Chem). The Phase II monotherapy trial (Lau et al., Lancet 2021) tested doses from 0.3 to 4.5 mg weekly in 706 adults with overweight and obesity over 26 weeks; the 4.5 mg dose produced a mean weight reduction of 10.8% versus 3.0% on placebo and 9.3% on liraglutide 3.0 mg daily. Doses through the studied range reduced weight by 6.0% to 10.8%.
After Phase II, Novo Nordisk prioritized the combination program. The REDEFINE 1 and REDEFINE 2 Phase III trials, published in NEJM in 2025, tested CagriSema (2.4 mg cagrilintide + 2.4 mg semaglutide weekly) against placebo and against the monotherapies in obesity and type 2 diabetes respectively. REDEFINE 1 reported a mean weight reduction of about 22.7% on CagriSema versus 16.1% on semaglutide alone and 11.8% on cagrilintide alone.
Standalone cagrilintide is not currently being progressed toward approval.
Regulatory status
Cagrilintide has no approved use, either as monotherapy or as part of CagriSema. Novo Nordisk has guided regulatory submissions for CagriSema in 2026 pending full Phase III analysis. There is no legitimate compounded supply; any vial sold for research is unregulated.
Mechanism
Amylin receptors are formed by the calcitonin receptor coupled to receptor activity-modifying proteins (RAMPs). Cagrilintide binds these complexes — particularly AMY1, AMY2, and AMY3 — with high affinity. The published mechanism papers describe three main effects:
- Suppression of postprandial glucagon, reducing hepatic glucose output after meals.
- Slowed gastric emptying, which prolongs satiety and blunts the postprandial glucose excursion.
- Central satiety signaling through receptors in the area postrema and other hindbrain regions; this is mechanistically distinct from GLP-1 appetite signaling, which is why combination with semaglutide produces additive effects in trials.
Cagrilintide also binds the calcitonin receptor itself with low affinity, which is hypothesized to contribute to its bone-related effects in preclinical work.
Half-life and dosing intervals
The published terminal half-life is approximately 6 to 7 days, supporting once-weekly subcutaneous injection. Steady state is reached after roughly 5 to 6 weeks.
In the Phase II trial, the maintenance doses tested were 0.3, 0.6, 1.2, 2.4, and 4.5 mg weekly, each reached through a four-week escalation. In the REDEFINE program the CagriSema dose was fixed at 2.4 mg of each component weekly, with escalation over 16 weeks. There is no established outside-of-trial dose.
Reconstitution example
Research-grade cagrilintide is supplied lyophilized in 2.4 mg vials matched to the CagriSema combination dose.
A 2.4 mg vial reconstituted with 1 mL of bacteriostatic water yields 2.4 mg/mL. On a 1 mL U-100 insulin syringe, 25 units (0.25 mL) contains 0.6 mg — one of the lower doses used in the Phase II escalation. Vial's calculator handles unit-to-mg conversion automatically.
What to know
- Investigational only. No regulator has approved cagrilintide for any use. Long-term safety data outside the Phase III combination program is limited.
- Combination is the lead program. Most of the late-stage data comes from CagriSema; standalone cagrilintide is not currently progressing toward approval.
- GI side effects. Phase II reported nausea in roughly 30% of participants on the higher doses, with most events mild and concentrated during escalation.
- Mechanism is distinct from GLP-1. Amylin signaling targets different brain regions than GLP-1, which is the rationale for combining the two.
- Storage. Lyophilized peptide is best stored refrigerated and protected from light. Once reconstituted, refrigerate and use within the stability window specified by the supplier.
Sources
- 1.Lau DCW et al. (2021). Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. The Lancet.
- 2.Garvey WT et al. (2025). Cagrilintide–Semaglutide for Weight Reduction (REDEFINE 1). New England Journal of Medicine.
- 3.Davies MJ et al. (2025). Cagrilintide–Semaglutide for Type 2 Diabetes and Weight Reduction (REDEFINE 2). New England Journal of Medicine.
- 4.Kruse T et al. (2021). Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of Medicinal Chemistry.