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Commonly combined with ChemAesthetic Cagrilintide 10mg in research protocols.
Ratings are based on published research data and are for informational purposes only.
Cagrilintide is a long-acting amylin analogue developed by Novo Nordisk, currently in Phase III clinical trials as CagriSema (combined with semaglutide). Phase II data demonstrate up to 15.6% body weight reduction as monotherapy over 26 weeks. Its weekly dosing schedule and complementary mechanism to GLP-1 agonists make it a subject of intensive combination obesity research.
Research Post
Cagrilintide (AM833) is a long-acting acylated analogue of human amylin developed by Novo Nordisk. Amylin (islet amyloid polypeptide, IAPP) is a peptide co-secreted with insulin from pancreatic β-cells that plays complementary roles to insulin in postprandial glucose regulation. Cagrilintide achieves once-weekly dosing through fatty acid acylation for albumin binding — analogous to the technology used in semaglutide — and is currently in Phase III trials in combination with semaglutide as CagriSema for obesity treatment.
Amylin is co-released with insulin in a 1:100 molar ratio from pancreatic β-cells in response to meals. It acts on amylin receptors (calcitonin receptor + RAMP1/2/3 co-proteins) in the area postrema, hypothalamus, and brainstem to exert complementary glycaemic effects:
In type 2 diabetes and obesity, amylin signalling is deficient (β-cell amylin secretion is reduced) or disrupted (IAPP aggregation and β-cell toxicity). Pramlintide (Symlin), a first-generation amylin analogue, was FDA-approved in 2005 for type 1 and type 2 diabetes but required three-times-daily injection — a major compliance limitation that cagrilintide's weekly dosing addresses.
Cagrilintide's C18 fatty diacid modification enables albumin binding analogous to semaglutide, extending half-life to approximately 7-8 days. Phase I data (Gall et al., 2020, Diabetes, Obesity and Metabolism) demonstrated dose-dependent body weight reduction of up to 8.0% over 26 weeks at 4.5 mg/week, with dose-dependent nausea as the primary adverse effect — consistent with amylin receptor activation in the area postrema.
The combination of cagrilintide with semaglutide (GLP-1 receptor agonist) in the CagriSema programme represents a mechanistically rational dual hormone strategy targeting complementary satiety pathways:
Phase II SCALE data showed CagriSema produced weight loss of approximately 15.6% over 32 weeks at full doses — exceeding either agent alone and consistent with additive or synergistic satiety mechanisms. Phase III REDEFINE trials are ongoing and represent the leading edge of obesity pharmacotherapy research.
A critical research question for obesity treatments is the ratio of fat mass to lean mass loss. Preliminary data suggests amylin-based approaches may preferentially preserve lean mass compared to GLP-1-only approaches — potentially due to amylin receptor expression in muscle and distinct energy substrate selection signalling. Research comparing body composition changes between amylin analogue, GLP-1 RA, and combination strategies is ongoing.
