Amylin receptor agonist

Cagrilintide is a long-acting analogue of amylin, the pancreatic hormone co-secreted with insulin that signals meal-related satiety. It works on its own - the phase 2 trial gave up to 10.8% weight loss at 4.5 mg over 26 weeks, beating daily liraglutide 3.0 mg at 9.0% - but it is being developed primarily as half of CagriSema, a fixed combination with semaglutide. That combination gave 20.4% weight loss at 68 weeks against 3.0% on placebo in REDEFINE 1, and 13.7% against 3.4% in people with type 2 diabetes. The interest in amylin is that it suppresses appetite by a different route from GLP-1, so the two add up rather than overlap - and in eloralintide's phase 2 trial the amylin mechanism alone reached 20%.

Eloralintide is a selective amylin receptor agonist - selective being the operative word, since amylin signals through receptor complexes built on the calcitonin receptor and earlier analogues hit both. Its phase 2 trial is the reason the amylin class is now taken seriously on its own: 48 weeks of once-weekly dosing produced mean weight reductions of 18% at 6 mg and 20% at 9 mg, against 0.4% on placebo. That is semaglutide territory, reached without touching the GLP-1 receptor at all. The adverse-effect profile is also different rather than simply lighter: nausea peaked at 64% in one dose group, and fatigue - which is not a prominent incretin effect - reached 43-46% at the higher doses. There is no phase 3 data, and no cardiovascular or long-term evidence of any kind.