Cagrilintide

Cagrilintide is a long-acting, acylated analog of human amylin (islet amyloid polypeptide, IAPP) developed by Novo Nordisk for the treatment of obesity. Native amylin is a 37-amino acid peptide co-secreted with insulin from pancreatic beta cells that acts as a satiety signal, slows gastric emptying, and suppresses postprandial glucagon secretion. Cagrilintide incorporates amino acid substitutions and a C18 fatty diacid side chain that extends its pharmacokinetic half-life to support once-weekly subcutaneous dosing, overcoming the rapid degradation that limits the therapeutic utility of native amylin.

Clinical trials have demonstrated that cagrilintide produces significant, dose-dependent reductions in body weight in individuals with overweight or obesity. The peptide exerts its effects through activation of amylin receptors (AMY1, AMY2, AMY3), which are heterodimers of the calcitonin receptor with receptor activity-modifying proteins (RAMPs). Activation of these receptors in the area postrema and nucleus tractus solitarius of the brainstem reduces food intake through central satiety signaling. Cagrilintide has also been investigated in combination with semaglutide (a GLP-1 receptor agonist) under the combination name CagriSema, which has shown additive weight loss effects.

Preclinical research has characterized cagrilintide's pharmacological profile across multiple amylin and calcitonin receptor subtypes. The molecule demonstrates potent agonism at amylin receptors with a selectivity profile designed to minimize calcitonin receptor-mediated side effects. Research interest extends to its potential metabolic effects beyond weight loss, including improvements in glycemic control and cardiovascular risk markers.