Cagrilintide
Also known as: NN9838, AM833
Investigational Compound. This compound is currently in clinical development and has not received regulatory approval. No established commercial regimen exists. Consult a qualified clinician for the latest information on clinical trial availability.
Overview
Clinical Summary
Cagrilintide is a long-acting amylin analogue developed by Novo Nordisk. Amylin is a pancreatic hormone co-secreted with insulin that promotes satiety, slows gastric emptying, and suppresses glucagon secretion. Cagrilintide is designed for once-weekly subcutaneous injection and is being studied both as monotherapy and in combination with semaglutide (CagriSema).
Plain Language Summary
Cagrilintide is an investigational medication that mimics a natural hormone called amylin, which helps you feel full after eating. It is being developed as a once-weekly injection for weight management. It is also being studied in combination with semaglutide (a GLP-1 medication) under the name CagriSema, which may produce greater weight loss than either drug alone.
Mechanism of Action
Cagrilintide is an acylated analogue of human amylin (islet amyloid polypeptide) with an extended half-life enabling weekly dosing. It activates amylin receptors (AMY1, AMY2, AMY3) in the area postrema and other brainstem nuclei to reduce food intake. It also activates calcitonin receptors. The primary mechanisms of weight loss include: reduced appetite via central satiety signaling, delayed gastric emptying, and suppression of postprandial glucagon secretion. The amylin pathway is complementary to GLP-1 signaling, providing the rationale for combination therapy.
Evidence Summary
Phase 2 data showed dose-dependent weight loss of up to 10.8% at 26 weeks as monotherapy. The combination of cagrilintide 2.4 mg + semaglutide 2.4 mg (CagriSema) showed approximately 15.6% weight loss at 32 weeks in a Phase 2 trial (REDEFINE program). Phase 3 REDEFINE trials are ongoing for CagriSema in obesity and T2D. Novo Nordisk has projected CagriSema as a potential successor to semaglutide monotherapy (Wegovy).
Safety Profile
GI adverse events are the most common class effect. Nausea, vomiting, and diarrhea were reported at higher rates during dose escalation but tended to attenuate over time. Injection site reactions occurred at a higher rate than with semaglutide alone. No signal for pancreatitis or thyroid C-cell tumors has emerged in clinical data to date, though the amylin class carries theoretical risk given calcitonin receptor activation.
Contraindications
- Known hypersensitivity to amylin analogues
- Gastroparesis or severe GI motility disorders
- Pregnancy (insufficient data)
Adverse Events
- Nausea
- Vomiting
- Diarrhea
- Injection site reactions (induration, erythema)
- Constipation
- Abdominal pain
Interactions
- May slow absorption of oral medications
- Additive GI effects with GLP-1RAs in combination
- Use caution with insulin (hypoglycemia risk)
Regulatory Notes
Cagrilintide is an investigational agent under development by Novo Nordisk. It has not received standalone FDA or EMA approval. The combination product CagriSema is in Phase 3 trials. Regulatory submissions may be expected following completion of the REDEFINE program.
Monitoring Considerations
Standard metabolic monitoring (HbA1c, fasting glucose, lipid panel). Monitor GI tolerability during dose escalation. Assess injection site reactions. Weight tracking at regular intervals.
These are general considerations for clinical awareness and do not constitute prescriptive monitoring recommendations for any individual patient.
Stability and Handling Notes
Investigational product. Not commercially available. Stability data governed by clinical trial protocols.
References
- 1RCT
Once-Weekly Cagrilintide for Weight Management in People with Overweight and Obesity
Enebo LB, Berthelsen KK, Kankam M, et al. (2021). New England Journal of Medicine
Key findings: Phase 2 trial. Dose-dependent weight loss up to 10.8% at 26 weeks with cagrilintide monotherapy.
Limitations: 26-week duration. Small sample size per dose group.
View source - 2RCT
CagriSema Phase 2 Trial: Cagrilintide Plus Semaglutide for Weight Loss
Frias JP, Deenadayalan S, Erichsen L, et al. (2023). Nature Medicine
Key findings: CagriSema achieved approximately 15.6% weight loss at 32 weeks vs 5.1% cagrilintide and 8.0% semaglutide alone.
Limitations: Phase 2 study. Open-label dose escalation phase followed by randomized period.
View source - 3review
Amylin Analogues for the Treatment of Obesity: From Pramlintide to Cagrilintide
Mathiesen DS, Bagger JI, Knop FK, et al. (2022). Diabetes, Obesity and Metabolism
Key findings: Review of amylin biology and the rationale for long-acting amylin analogues in obesity treatment.
Limitations: Narrative review.
Last reviewed: 2024-11-20 | Version: 1 | Status: Published
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