Cagrilintide
Also known as: AM833, NNC0174-0833, Long-acting amylin analogue
A long-acting amylin analogue studied for its effects on satiety signalling and body weight, alone and alongside GLP-1 receptor agonists.
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Molecular Data
- Class
- Long-acting amylin analogue / amylin (AMY) and calcitonin receptor agonist
- Molecular Weight
- ~3,951 Da
- Molecular Formula
- Acylated peptide analogue — no single empirical formula is published in standard references
- Half-Life
- Several days — long enough to support once-weekly subcutaneous dosing in clinical trials
Mechanism of Action
Amylin is a 37-amino-acid hormone co-secreted with insulin by pancreatic beta cells. Native amylin has a half-life of minutes and readily forms amyloid fibrils, which makes it impractical as a research compound. Cagrilintide is an engineered analogue built to solve both problems.
- Amylin and calcitonin receptor agonism: Cagrilintide activates the amylin receptor complexes (AMY, formed by the calcitonin receptor in combination with receptor activity-modifying proteins) and the calcitonin receptor itself, with picomolar potency in reporter assays.
- Fatty-diacid acylation: A fatty-diacid side chain promotes reversible albumin binding, which slows renal clearance and extends the circulating half-life from minutes to days — the basis for once-weekly subcutaneous dosing in trials.
- Fibrillation-resistant backbone: The peptide backbone was based on a pramlintide-like analogue rather than on human amylin specifically to reduce fibril formation in solution.
- Complementary to incretin signalling: Amylin signalling acts largely through hindbrain circuits distinct from the GLP-1 pathway, which is the rationale for the combination research pairing cagrilintide with semaglutide.
Research History
Amylin pharmacology has a long history: pramlintide, a fibrillation-resistant amylin analogue, was approved in 2005 but required dosing with each meal, limiting its practical use.
Cagrilintide was developed at Novo Nordisk as a once-weekly successor. Kruse and colleagues published the medicinal-chemistry programme in 2021, describing how acylation attachment points were screened by receptor binding and potency before the final candidate was selected.
A phase 2 dose-finding trial reported by Lau and colleagues in 2021 randomised 706 participants across cagrilintide doses of 0.3–4.5 mg, with liraglutide 3.0 mg as an active comparator and placebo, over a 26-week treatment period at 57 sites in ten countries. A separate phase 1b trial by Enebo and colleagues examined cagrilintide given concomitantly with semaglutide 2.4 mg — the combination later developed under the name CagriSema. Cagrilintide is not approved as a standalone product and remains an investigational compound.
Notable Studies
Kruse T, Hansen JL, Dahl K, Schäffer L, Sensfuss U, Poulsen C, et al. · Journal of Medicinal Chemistry
The originator's medicinal-chemistry account of how cagrilintide was designed: screening acylation attachment points for receptor potency, and choosing a pramlintide-like backbone to limit fibril formation.
Lau DCW, Erichsen L, Francisco AM, et al. · The Lancet
906 participants randomised across cagrilintide 0.3–4.5 mg, liraglutide 3.0 mg, and placebo over 26 weeks of treatment plus 6 weeks of follow-up, at 57 sites in ten countries. Reported dose-dependent bodyweight reduction and acceptable tolerability.
Enebo LB, Berthelsen KK, Kankam M, et al. · The Lancet
Multiple-ascending-dose phase 1b trial in participants with BMI 27.0–39.9 kg/m². The origin of the combined amylin-plus-incretin research line later developed as CagriSema.
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