Cagrilintide is a synthetic long-acting amylin analogue developed by Novo Nordisk, engineered for once-weekly subcutaneous dosing. Amylin is a 37-amino-acid neuroendocrine peptide co-secreted with insulin from pancreatic β-cells; it regulates postprandial glucagon, gastric emptying and satiety. Cagrilintide is studied both as a monotherapy weight-management compound and — more prominently — as the partner of semaglutide in the dual-mechanism CagriSema research programme, which has reported some of the largest weight-loss effects observed in the GLP-1 / amylin combination class.
Cagrilintide is an agonist at the three amylin receptors AMY₁, AMY₂ and AMY₃, which are heterodimeric complexes of the calcitonin receptor with receptor activity-modifying proteins 1, 2 and 3. The principal sites of action relevant to weight-management research are the area postrema and dorsal motor nucleus of the vagus in the brainstem, where amylin signalling drives satiety and slows gastric emptying.
The acylated long-acting backbone (an analogue strategy similar to that used for semaglutide and tirzepatide) extends the plasma half-life to approximately 7 days, supporting once-weekly research dosing. Compared with shorter-acting amylin analogues (pramlintide), cagrilintide's pharmacokinetic profile permits dosing frequencies compatible with GLP-1 partner compounds.
The CagriSema research thesis is that amylin and GLP-1 act on partially non-overlapping satiety pathways — amylin acting predominantly via the brainstem, GLP-1 via additional hypothalamic and vagal circuits — and combining them produces additive or synergistic weight-loss effects exceeding either monotherapy.
The CagriSema programme (cagrilintide 2.4 mg + semaglutide 2.4 mg) is the most studied amylin/GLP-1 combination in development. A Phase 2 trial (Lancet, 2021) in adults with overweight/obesity reported approximately 17% weight loss at 20 weeks with the combination versus approximately 8% with semaglutide alone — establishing the additive-effect thesis.
The pivotal Phase 3 REDEFINE programme continues to read out. The combination is widely viewed as a candidate to challenge tirzepatide on weight-loss magnitude.
Cagrilintide monotherapy at 2.4 mg weekly produced approximately 10% weight loss in Phase 2 (Diabetes, Obesity & Metabolism, 2021) — substantial but less than GLP-1 monotherapy. The compound's interest is primarily as a combination partner rather than as a standalone weight-management compound.
Beyond weight management, amylin pathway research has applications in postprandial glucagon control in type 1 diabetes (the original pramlintide indication) and emerging interest in neurodegenerative research where amylin-pathway dysregulation has been documented in Alzheimer's disease preclinical models.