Cagrilintide

Cagrilintide is a long-acting analog of human amylin (islet amyloid polypeptide, IAPP), a peptide co-secreted with insulin from pancreatic beta cells that contributes to postprandial glucose control and satiety signaling. Native amylin's extremely short half-life and amyloid-forming tendency necessitated extensive modifications to create a therapeutic candidate.

The compound incorporates structural modifications that prevent the amyloid fibril formation responsible for pancreatic islet deposition in type 2 diabetes, combined with fatty acid acylation that enables albumin binding and once-weekly dosing. This creates a long-acting amylin agonist suitable for chronic administration.

Amylin receptors (AMY1, AMY2, AMY3 - composed of calcitonin receptor with RAMP proteins) are expressed in the area postrema and other brain regions controlling appetite. Activation produces satiety signaling distinct from and complementary to GLP-1 pathway effects, supporting the combination therapy approach under clinical investigation.

Cagrilintide is being developed in combination with semaglutide (CagriSema) to achieve greater weight loss than either agent alone. The rationale combines two physiological satiety signals - amylin and GLP-1 - that normally work together to regulate energy intake. Early clinical research shows promising additive effects on body weight.