Cagrilintide

Amylin (islet amyloid polypeptide) is a 37-residue hormone co-secreted with insulin. Native human amylin is notoriously difficult to work with: it is strongly amyloidogenic, aggregating into fibrils — the same fibrils found in the pancreatic islets of type 2 diabetes, which is how it was discovered.

Cagrilintide (AM833) is an engineered analogue that resists aggregation while retaining receptor activity, with acylation for albumin binding and weekly dosing. Solving the aggregation problem is the core of what makes it a usable molecule.

Amylin acts at receptors formed from the calcitonin receptor paired with receptor activity-modifying proteins, concentrated in the area postrema — a hindbrain region outside the blood-brain barrier that samples circulating signals directly.

That pathway is independent of GLP-1 receptor signalling, and the independence is the entire pharmacological argument for the compound:

• Satiety signalling through calcitonin-family receptors rather than incretin receptors

• Gastric emptying, slowed by a mechanism separate from GLP-1's

• Glucagon suppression, an amylin action established long before this analogue

• Amyloid aggregation biology, where the engineering itself is the subject

• Combination pharmacology — whether two independent satiety routes are additive

Cagrilintide has been studied as a single agent in phase 2 obesity trials, and far more extensively in combination with semaglutide as CagriSema. Its standalone data is the less developed half of its literature, and for most research purposes it functions as the amylin component of a combination rather than as a candidate in its own right.

It is not approved in any jurisdiction.

Supplied as a lyophilised powder. Amylin analogues are engineered against aggregation but reconstitution should still be gentle, and preparations should be inspected for cloudiness or visible particulate before use — with this class specifically, aggregation is the failure mode to look for. Store refrigerated and protected from light.

CagriSema is the fixed combination with semaglutide and the context most of this compound's data comes from. Semaglutide is the incretin half of that pairing.