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Cagrilintide and semaglutide work through different mechanisms and have different dosing schedules: Cagrilintide: Amylin receptor agonist Escalation: 0.6 mg 1.2 mg 2.4 mg weekly Three-step titration over 8 weeks Semaglutide: GLP-1 receptor agonist Escalation: 0.25 mg 0.5 mg 1.0 mg 1.7 mg 2.4 mg weekly Five-step titration over 16-20 weeks When combined in CagriSema, both peptides are dosed at 2.4 mg weekly, representing the maximum studied dose for each component

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Receptor desensitization and adaptation GLP-1 receptors can become temporarily desensitized when exposed to high agonist concentrations too quickly

Other diabetes medication classes offer alternatives if GLP-1 therapy proves unsuitable: SGLT2 inhibitors (such as dapagliflozin or empagliflozin) provide cardiovascular and renal benefits without affecting gastric emptying, though require adequate renal function and carry risks of genital infections and diabetic ketoacidosis DPP-4 inhibitors (such as sitagliptin) work on the incretin system but with less pronounced gastrointestinal effects note these should not be combined with GLP-1 receptor agonists Traditional agents including metformin, sulfonylureas, or insulin may be appropriate depending on individual circumstances Any medication change should be made in consultation with your diabetes specialist or GP, considering your overall glycaemic control, cardiovascular risk profile, and treatment goals, in line with NICE NG28 guidance

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