Cagrilinitide

Cagrilinitide (AM833) is a long-acting amylin analog developed by Novo Nordisk. Amylin is a peptide hormone co-secreted with insulin from pancreatic beta cells that plays roles in satiety, gastric emptying, and glucagon suppression. Cagrilinitide has a prolonged half-life suitable for once-weekly subcutaneous dosing. In combination with CagriSema, semaglutide, Tirzepatide or Retatrutide, it has demonstrated additive weight loss effects in clinical trials.

— 5 mg Vial —

Reconstitute: Add 2.0 mL bacteriostatic water → ~2.5 mg/mL concentration.
Typical weekly range: 0.2–2.7 mg once weekly (gradual titration over 4–6 weeks).
Easy measuring: At 2,5 mg/mL, 1 unit = 0.01 mL ≈ 0.02.5 mg (25 mcg) on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, use within 30 days.

Schedule: Weekly subcutaneous injections for 12–16 weeks.
Goal: Support satiety, reduce food intake, and promote weight management over time.

— 10 mg Vial —

Reconstitute: Add 2.0 mL bacteriostatic water → ~5 mg/mL concentration.
Typical weekly range: 0.2–2.7 mg once weekly (gradual titration over 4–6 weeks).
Easy measuring: At 5 mg/mL, 1 unit = 0.01 mL ≈ 0.05 mg (50 mcg) on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, use within 30 days.

Schedule: Weekly subcutaneous injections for 12–16 weeks.
Goal: Support satiety, reduce food intake, and promote weight management over time.

• Significant weight reduction in clinical trials
• Reduces appetite and food intake via hypothalamic amylin receptors
• Slows gastric emptying, extending satiety
• Suppresses postprandial glucagon secretion
• Improves glycemic control in type 2 diabetes
• Additive weight loss when combined with semaglutide (CagriSema combination)
• Once-weekly dosing improves compliance
• Reduces body fat mass while preserving lean mass relative to body weight loss

Cagrilinitide binds to amylin receptors (AMY1-3), which are complexes of the calcitonin receptor with receptor activity-modifying proteins (RAMPs). Amylin receptor activation in the area postrema and hypothalamus reduces food intake and slows gastric emptying. Cagrilinitide also suppresses glucagon secretion from pancreatic alpha cells in a glucose-dependent manner, contributing to glycemic control. Its extended half-life (achieved via fatty acid conjugation) allows once-weekly administration, similar to semaglutide.

• Nausea and vomiting — most common, especially during titration
• Decreased appetite
• Diarrhea or constipation
• Injection site reactions
• Headache
• Hypoglycemia when combined with insulin secretagogues

Slow dose escalation over several weeks minimizes GI side effects. Take with food if nausea is problematic. Stay well hydrated. Monitor blood glucose when combining with other antidiabetic agents. Injection site rotation minimizes local reactions.

• Personal or family history of medullary thyroid carcinoma
• Multiple Endocrine Neoplasia syndrome type 2
• Pregnancy and lactation
• Pancreatitis history
• Severe GI dysmotility

• Enebo LB et al. (2021). Safety, tolerability, pharmacokinetics, and pharmacodynamics of cagrilinitide. The Lancet Diabetes & Endocrinology. DOI: 10.1016/S2213-8587(21)00249-5
• Frias JP et al. (2023). Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes. NEJM. DOI: 10.1056/NEJMoa2307384