Research Peptide · For laboratory research use only
Also known as AM833, Long-acting amylin analogue
Cagrilintide (AM833) is a stable, lipidated, long-acting analogue of amylin, a pancreatic hormone. Native amylin has a strong tendency to form amyloid fibrils, which makes it a difficult starting point for drug design; the structure-activity work that led to cagrilintide was published in 20211.
It is a non-selective agonist of the amylin receptors (AMY1R, AMY2R and AMY3R, which are heterodimers of the calcitonin receptor with receptor activity-modifying proteins) and of the calcitonin receptor itself2,3. Research has spanned receptor pharmacology, cryo-electron microscopy, rodent studies of energy balance and registered clinical trials2,3,4,5,6,7.
As described in the research literature
As described in the research literature, cagrilintide was profiled across 25 pharmacological endpoints covering receptor binding, activation and regulation, and compared with selective and non-selective amylin and calcitonin receptor agonists; the authors described a pharmacological profile distinct from each comparator2. Cryo-EM structures of cagrilintide bound to Gs-coupled AMY1R, AMY2R, AMY3R and the calcitonin receptor showed an amylin-like binding mode with distinct receptor conformational dynamics3.
In vivo work has examined where it acts. In high-fat-fed mice lacking RAMP1 and RAMP3, the body weight response to cagrilintide was impeded compared with wild-type littermates, and neuronal cFos activation was examined in the dorsal vagal complex and lateral parabrachial nucleus4. A cross-species transcriptomic atlas of the caudal brainstem identified Calcr/Prlh neurons in the nucleus of the solitary tract as mediators in rats, where knocking down prolactin-releasing hormone in the dorsal vagal complex abrogated the effects of cagrilintide but not semaglutide5.
What published studies have examined
The 2021 medicinal chemistry paper reports the structure-activity work behind cagrilintide, including lipidation to extend its duration of action and the challenge posed by the fibril-forming tendency of native amylin1.
Sources [1]
Binding, signalling and receptor regulation at amylin and calcitonin receptors were compared with pramlintide, salmon calcitonin, human calcitonin, rat amylin and two other lipidated analogues2. Cryo-EM structures and molecular dynamics examined how cagrilintide engages each receptor3.
RAMP1/3 knockout mice were used to test the dependence of cagrilintide on AMY1R and AMY3R4. Single-cell and spatial transcriptomics in rat, mouse and macaque brainstem, with chemogenetic and knockdown experiments in rats, identified neuronal populations in the dorsal vagal complex involved in its effects5.
Studies in rats examined cagrilintide combined with semaglutide, quantifying energy intake and energy expenditure against pair-fed and weight-matched controls6.
Sources [6]
A multicentre, randomised, double-blind, placebo-controlled and active-controlled phase 2 trial used percentage change in body weight from baseline to week 26 as its primary endpoint (NCT03856047)7.
Sources [7]
Development of Cagrilintide, a Long-Acting Amylin Analogue.
Kruse T, Hansen JL, Dahl K, et al. Journal of Medicinal Chemistry, 2021.
AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists.
Fletcher MM, Keov P, Truong TT, et al. The Journal of Pharmacology and Experimental Therapeutics, 2021.
Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors.
Cao J, Belousoff MJ, Johnson RM, et al. Nature Communications, 2025.
Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3.
Carvas AO, Leuthardt A, Kulka P, et al. EBioMedicine, 2025.
A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance.
Ludwig MQ, Coester B, Gordian D, et al. Nature Metabolism, 2026.
CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure.
Jacobsen JM, Halling JF, Blom I, et al. Nature Metabolism, 2025.
Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial.
Lau DCW, Erichsen L, Francisco AM, et al. The Lancet, 2021.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.