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Amylin and Calcitonin Receptor Agonism Cagrilintide Component Cagrilintide functions as a non-selective agonist at amylin receptors (AMY1R, AMY2R, AMY3R) and calcitonin receptor (CTR), inducing satiety through mechanisms distinct from but complementary to GLP-1 signaling: Area postrema activation in the brainstem inducing satiety signals Gastric emptying delay through mechanisms additive with GLP-1 effects Hypothalamic signaling affecting homeostatic energy balance regulation Nucleus accumbens modulation potentially affecting hedonic food intake Enhanced satiety duration providing prolonged appetite suppression Structural studies published in 2025 revealed that cagrilintide induces distinct conformational dynamics at calcitonin-family receptors compared to native amylin or other analogues, which may contribute to its exceptional clinical efficacy in combination with GLP1
Current guidelines recommend either class for people with type 2 diabetes mellitus and established ASCVD, high cardiovascular risk, HF, or CKD [84,85]
Importantly, tirzepatide carries a boxed warning for risk of thyroid C-cell tumors and is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
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