Cagrilintide: Complete Guide

Cagrilintide is a synthetic, acylated amylin analog designed for once-weekly subcutaneous injection. Native amylin (islet amyloid polypeptide/IAPP) is a 37-amino-acid peptide co-secreted with insulin from pancreatic beta cells after meals. It contributes to glucose homeostasis by slowing gastric emptying, suppressing postprandial glucagon, and promoting satiety through brainstem signaling.

The challenge with native amylin is its rapid degradation and tendency to aggregate. Cagrilintide overcomes these limitations through amino acid substitutions and fatty acid acylation, extending its half-life to support weekly dosing. Pramlintide (Symlin), the first-generation amylin analog, requires dosing with each meal — cagrilintide represents a significant pharmacokinetic advance.

Cagrilintide activates amylin receptors (AMY1, AMY2, AMY3) — heterodimers of the calcitonin receptor with receptor activity-modifying proteins (RAMPs):

• Area postrema signaling: Activates neurons in the area postrema and nucleus tractus solitarius to promote satiety and reduce food intake
• Gastric emptying: Slows gastric emptying, prolonging nutrient exposure and satiety signals
• Glucagon suppression: Reduces inappropriate postprandial glucagon secretion
• Complementary to GLP-1: The amylin pathway is distinct from GLP-1 signaling, enabling additive effects when combined (CagriSema)

In clinical trials, cagrilintide has been studied at doses of 0.3–4.5 mg weekly via subcutaneous injection. Dose escalation schedules are used to minimize gastrointestinal side effects. In the CagriSema combination, cagrilintide 2.4 mg is paired with semaglutide 2.4 mg in a single weekly injection.

Cagrilintide is not yet commercially available — dosing information is derived from published clinical trial protocols.

• Nausea: Most common adverse event, generally mild to moderate and decreasing over time
• Vomiting and diarrhea: GI effects consistent with amylin receptor activation
• Injection site reactions: Mild and transient
• Hypoglycemia: Low risk as monotherapy; risk increases in combination with insulin or sulfonylureas

Clinical trial safety data is still accumulating. Phase 3 results will provide a more complete safety profile.

Cagrilintide is typically discussed alongside GLP-1 agonists due to its role in CagriSema and its weight loss applications. For a comprehensive overview of the class, see the complete GLP-1 guide.

• Semaglutide (Ozempic/Wegovy): The GLP-1 agonist paired with cagrilintide in CagriSema. Clinical trials demonstrate 14.9% weight loss as monotherapy (STEP 1, Wilding et al., NEJM 2021), increasing to 22.7% in the CagriSema combination.
• Tirzepatide (Mounjaro/Zepbound): A dual GLP-1/GIP agonist achieving up to 22.5% weight loss — a different multi-pathway approach than CagriSema's amylin+GLP-1 mechanism.
• Retatrutide: The triple GLP-1/GIP/glucagon agonist with the highest trial weight loss recorded (24.2%). Represents yet another multi-target strategy.
• Survodutide and mazdutide: Dual GLP-1/glucagon agonists that add energy expenditure and liver fat reduction benefits through glucagon receptor activation.
• Liraglutide (Saxenda): The first-generation daily GLP-1 agonist. CagriSema represents a generational advance in both efficacy and convenience.