Cagrilintide: the amylin analogue that complements GLP-1 — Scientific guide

What is Cagrilintide?

Le Cagrilintide(search code)AM833) is a synthetic analogue ofAmyline, developed by Novo Nordisk. Amylin is a peptide hormone of 37 amino acids co-secreted with insulin by the beta cells of the pancreas after meals. It acts as asatiety signalcomplementary to that of GLP-1.

Native amylin is unstable and difficult to use in research: it aggregates rapidly and has a very short half-life. Cagrilintide was designed to solve these two problems through aacylated structure(grafting of a fatty acid chain) which extends its half-life to several days, making it compatible with protocols atweekly administration.

Mechanisms of action

Cagrilintide replicates and prolongs the natural signaling of amylin through several convergent pathways.

Central satiety

It activates amylin receptors in the nuclei of thebrainstem(area postrema) and of thehypothalamuskey regions for controlling food intake. This activation increases the feeling of satiety and reduces the amount of food ingested, without directly acting on the GLP-1 pathway.

Slowing of gastric emptying

Like endogenous amylin, Cagrilintide slows the rate at which food passes from the stomach to the intestine, prolonging the feeling of fullness after meals and mitigating postprandial blood sugar spikes.

Glucagon regulation

It reduces postprandial secretion ofglucagon, the hormone that raises blood sugar, thus contributing to glucose homeostasis in addition to its effect on appetite.

Dual activity amylin / calcitonin

The Cagrilintide is adual agonistamylin and calcitonin receptors. This dual affinity, combined with its prolonged half-life, distinguishes it from first-generation amylin analogues such as pramlintide, which have a short action.

CagriSema: association with semaglutide

The most studied research area concerning Cagrilintide is its fixed combination with thesemaglutide(GLP-1 agonist), calledCagriSemaThe logic is that of complementary approaches:

In Phase 2 studies, Cagrilintide monotherapy showed a body weight loss ofapproximately 10 to 11%at maximum dose. In combination with CagriSema, the most recent research programs report reductions of up to15 to 22%, placing this combination among the most promising in the field.

Technical specifications of the Cagrilintide

Reconstruction in research

Cagrilintide reconstitutes like a classic lyophilized peptide, at thebacteriostatic waterFor a 10 mg vial, adding 1 mL of solvent results in a working concentration of 10 mg/mL. Dissolution is achieved by allowing the water to flow down the side of the vial, without vigorous shaking. The solution remains stable for approximately 4 weeks at +2-8°C; repeated freeze-thaw cycles should be avoided.

Limitations and state of research

Cagrilintide is a recent molecule whose clinical development is ongoing:

• The data comes primarily from Phase 2 studies and ongoing Phase 3 programs.
• The long-term tolerance profile of the CagriSema combination is still being characterized.
• Gastrointestinal effects (nausea, excessive satiety) are the most frequently reported, as with other satiety peptides.
• Research product: no extrapolation to human use has been validated.