Amylin

Amylin

Amylin, also called islet amyloid polypeptide (IAPP), is a 37-amino-acid peptide hormone that pancreatic beta cells release together with insulin when you eat. Its actions complement insulin’s: amylin slows gastric emptying, lowers glucagon release after meals and curbs appetite by acting on receptors in the area postrema, the nucleus of the solitary tract and other brain regions.

Amylin signaling falls in type 2 diabetes (alongside insulin deficiency) and is partly missing in type 1 diabetes. Pramlintide, the first amylin analogue, was approved by the FDA in 2005 for type 1 and type 2 diabetes, but it was little used because of its short half-life, the need to inject it at every meal and tolerability problems.

Long-acting amylin analogues designed for once-weekly dosing in obesity have revived interest in amylin. Cagrilintide is the leading example, now combined with semaglutide as CagriSema (Novo Nordisk). The idea is that amylin and GLP-1 switch on separate, independent appetite pathways in the brain, so together they cut calorie intake more than either does alone. CagriSema reported -22.7% mean weight loss at 68 weeks in the REDEFINE-1 Phase 3 trial (published in NEJM), and an FDA New Drug Application was filed in December 2025.

Retatrutide does not act on the amylin receptor. Its triple-agonist design combines GLP-1, GIP and glucagon receptor activation to work on both energy intake and energy use. Comparing retatrutide with CagriSema shows a strategic choice in next-generation obesity drugs: suppress appetite through two pathways, or suppress appetite and raise energy use at the same time.