GLP-1 is not the only hormone that tells the brain a meal is over. Cagrilintide was built to study a second one, amylin, on its own and alongside semaglutide.
Cagrilintide · Long-acting amylin analogue
Appetite is shaped by more than one hormone. Amylin is released by the pancreas with insulin and contributes to satiety, the feeling of fullness that helps bring a meal to an end. Cagrilintide is a stabilised version of amylin developed to investigate that pathway. Evidence is from human trials in adults with overweight or obesity, most extensively in combination with the GLP-1 medicine semaglutide.
Cagrilintide is a synthetic analogue of amylin, a 37-amino-acid hormone that pancreatic beta cells release together with insulin after eating. Amylin acts on receptors in the brainstem and hypothalamus that are involved in satiety and in slowing stomach emptying; those receptors are formed from the calcitonin receptor combined with helper proteins, so cagrilintide is described as an amylin and calcitonin receptor agonist, a molecule that activates a receptor.
Native amylin is cleared within minutes and readily clumps into fibrils, which makes it awkward to study. Novo Nordisk altered several residues and attached a fatty-acid chain so the peptide binds albumin and stays in the blood for days, as described in the medicinal chemistry paper. The amylin pathway is separate from the incretin pathway that GLP-1 medicines use, which is why the two are studied together.
Cagrilintide alone was tested in a 26-week phase 2 dose-finding trial in 706 adults with overweight or obesity, without diabetes, given by subcutaneous injection with placebo and liraglutide as comparators. Weight reduction was greater than placebo at every dose, and gastrointestinal effects and injection-site reactions were the most common adverse events (Lau et al., 2021).
The combination with semaglutide, known as CagriSema, was first examined in a phase 1b safety and pharmacokinetics study (Enebo et al., 2021) and then in REDEFINE 1, a 68-week phase 3a trial in 3,417 adults with obesity, or overweight with a related condition, without diabetes. Participants received the two peptides given together once weekly by subcutaneous injection, semaglutide alone, cagrilintide alone, or placebo, all with lifestyle support. Mean weight change was about 20% with the combination against 3% with placebo; the main comparison was with placebo, with the smaller single-agent arms reported alongside it. REDEFINE 2 tested the same combination in adults with type 2 diabetes (Davies et al., 2025). Gastrointestinal adverse events affected about four in five participants on the combination (Garvey et al., 2025). No human trial has examined cagrilintide with tirzepatide or retatrutide.
Cagrilintide's own contribution is harder to read than the combination's. The single-agent arm of REDEFINE 1 was small, and the phase 2 trial ran for 26 weeks, so long-term effects of amylin agonism on its own are not well described.
Combination evidence is specific to semaglutide. A 2026 study in obese male rats reported additive effects of cagrilintide with retatrutide (Petersen et al.); that is an animal finding, not evidence in people. All human data come from sponsor-run trials of a pharmaceutical formulation with lifestyle support; research material is not that formulation.
Cagrilintide is an investigational compound. It is not an approved medicine in Australia and has not been approved by any regulator, alone or in the CagriSema combination.
Sources and status checked 2026-09-23
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