Incretin and amylin
Cagrilintide vs Semaglutide: Research Comparison
Cagrilintide and semaglutide act on different hormone receptors. Cagrilintide is a long-acting analogue of amylin, a hormone made by the pancreas. Semaglutide is a long-acting analogue of GLP-1, a hormone released by the gut. The two have been tested together in human trials under the name CagriSema.
Side-by-side comparison
| Attribute | Cagrilintide | Semaglutide |
|---|---|---|
| What it is | Long-acting amylin analogue with a fatty-acid chain | Long-acting GLP-1 analogue with a fatty-acid chain |
| Receptors | Amylin receptors (calcitonin receptor plus RAMP) and the calcitonin receptor | GLP-1 receptor |
| Developer | Novo Nordisk | Novo Nordisk |
| Human data | Phase 2 trial on its own (706 adults); phase 3 trials mostly combined with semaglutide | Large randomised trials (SUSTAIN, STEP, SELECT) |
| Licensed status | Not licensed in the UK, EU or US | Licensed as a prescription medicine in the UK, EU and US |
Detailed analysis
Cagrilintide (AM833) is a synthetic analogue of amylin, a 37-amino-acid hormone made by the insulin-producing beta cells of the pancreas. Natural amylin clumps into fibres, so cagrilintide was redesigned to be stable and given a fatty-acid chain to make it long-acting. In cell studies it activates amylin receptors and the calcitonin receptor. In rats, long-term treatment changed gene activity in brainstem nerve cells in the nucleus of the solitary tract (Ludwig et al., 2026).
Semaglutide differs from human GLP-1 at two positions and carries a fatty-acid chain, so it binds albumin and lasts much longer than natural GLP-1 (Lau et al., 2015). It activates the GLP-1 receptor, which increases insulin release when blood glucose is high, lowers glucagon release and slows stomach emptying. In rats and mice it did not cross the blood-brain barrier but reached brain areas next to it (Gabery et al., 2020).
Cagrilintide was tested on its own in a phase 2 placebo-controlled trial in 706 adults (Lau et al., 2021); most phase 3 trials test it combined with semaglutide (Garvey et al., 2025). Semaglutide is a licensed medicine and cagrilintide is not. The research material supplied here is not a licensed medicine.
Key differences
- ·Cagrilintide acts on amylin and calcitonin receptors; semaglutide acts on the GLP-1 receptor.
- ·Semaglutide is a licensed prescription medicine; cagrilintide is investigational.
- ·Cagrilintide's phase 3 trials mostly test it in combination with semaglutide.
- ·In rats, blocking one brainstem gene (Prlh) stopped cagrilintide's effects but not semaglutide's, pointing to different brain pathways.
Research summary
Both are long-acting peptides from Novo Nordisk that act on different receptors. Semaglutide has large randomised trials behind its licences. Cagrilintide has a phase 2 trial on its own (Lau et al., 2021) and phase 3 trials mostly in combination (Garvey et al., 2025); its long-term safety on its own is not known. Supplied for laboratory research use only.