Cagrilintide

Historical Background

Cagrilintide is a long-acting amylin analogue developed by Novo Nordisk, designed to mimic the satiety hormone amylin (IAPP — islet amyloid polypeptide) secreted by pancreatic beta cells alongside insulin. Unlike native amylin, cagrilintide is engineered for once-weekly subcutaneous dosing through fatty acid chain modifications that extend its half-life to approximately 7 days. It is the amylin component of the investigational combination Cagrisema (cagrilintide + semaglutide), which has demonstrated superior weight loss compared to either compound alone.

What It's Used For

• Amylin receptor (AMY1–AMY3) agonism research
• Appetite and satiety regulation studies
• Dual amylin + GLP-1 receptor co-stimulation research (with semaglutide)
• Gastric emptying and food intake models
• Obesity and metabolic syndrome research
• Complementary mechanism to GLP-1 agonists

Positive Effects

• Activates amylin receptors in the hypothalamus and brainstem to reduce food intake
• Slows gastric emptying — prolongs satiety independently of GLP-1
• Reduces glucagon secretion post-meal (complementary to GLP-1R effects)
• REDEFINE 1 trial (cagrilintide 2.4 mg + semaglutide 2.4 mg): ~25% mean weight loss — exceeding either drug alone
• Addresses different hypothalamic satiety circuits than GLP-1, enabling additive appetite suppression
• Improves postprandial glycemic control

Potential Side Effects

• Nausea, vomiting, diarrhea (amylin receptor activation)
• Injection site reactions
• Hypoglycemia risk in combination with insulin or sulfonylureas
• GI effects generally similar in profile to GLP-1 agonists

Administration

Subcutaneous injection. Clinical research dose-escalation: 0.3 mg → 0.6 mg → 1.2 mg → 2.4 mg over 16 weeks. Reconstitute with bacteriostatic water; store at 2–8°C. Most commonly studied in combination with semaglutide. Once-weekly dosing due to extended half-life.