CagriSema

Cagrilintide–Semaglutide (CagriSema) is a fixed-dose combination of the long-acting amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide. It is being developed by Novo Nordisk as a once-weekly subcutaneous therapy for chronic weight management and type 2 diabetes. By combining two distinct but complementary mechanisms of action on glycaemic control and body weight, CagriSema represents a novel approach to metabolic disease research.

CagriSema exerts its effects through simultaneous activation of two complementary receptor pathways. Cagrilintide is a long-acting acylated amylin analogue that acts as a nonselective agonist for amylin receptors (AMYR) and calcitonin G protein-coupled receptors (CTR). This activation reduces food intake and promotes weight loss through central and peripheral mechanisms. Semaglutide is a long-acting, selective GLP-1 receptor agonist that promotes insulin secretion, inhibits gastric emptying and appetite, enhances autophagy, inhibits oxidative stress and apoptosis, and regulates mitochondrial function and lipid metabolism. Together, these agents provide complementary effects on energy intake, appetite control, and glycaemic regulation.

• Obesity and Weight Management: Investigated for significant and sustained weight reduction in adults with overweight or obesity. In the REDEFINE 1 phase 3a trial, CagriSema (2.4 mg/2.4 mg) demonstrated superior weight loss compared to semaglutide monotherapy and placebo. A once-weekly fixed-dose combination led to an average weight loss of −13.7%, compared to −3.4% with placebo, with 84% achieving ≥5% weight loss. A 32-week trial showed mean body weight change of −15.6% with CagriSema vs −5.1% with semaglutide.
• Type 2 Diabetes Mellitus: Studied for glycaemic control in adults with type 2 diabetes. In the REIMAGINE 1 trial, CagriSema (2.4 mg each) achieved an estimated mean HbA1c reduction of −1.8 percentage points after 40 weeks. In the REIMAGINE 3 trial as an add-on to basal insulin, CagriSema (2.4 mg each) demonstrated a mean HbA1c reduction of −2.33%.
• Cardiometabolic Outcomes: Investigated for blood pressure reduction and broader cardiometabolic benefits in adults with overweight or obesity.
• Appetite and Energy Intake Studies: Employed to evaluate effects on ad libitum energy intake, craving control, hunger, satiety, and gastric emptying. Studies demonstrate CagriSema significantly reduces energy intake (63% reduction) and appetite without delaying gastric emptying.

Peptide Content: Cagrilintide and Semaglutide (fixed-dose combination per vial; concentrations vary by research protocol, e.g., 2.4 mg/2.4 mg or 1.0 mg/1.0 mg)
CAS Number: 1415456-99-3 (Cagrilintide); 910463-68-2 (Semaglutide)
Molecular Formula: C₁₉₄H₃₁₂N₅₄O₅₉S₂ (Cagrilintide); C₁₈₇H₂₉₁N₄₅O₅₉ (Semaglutide)
Molecular Weight: 4,409.01 g/mol (Cagrilintide); 4,113.58 g/mol (Semaglutide)
Sequence (Cagrilintide): {Eicosanedioic acid-γ-Glu}-Lys-Cys-Asn-Thr-Ala-Thr-Cys-Ala-Thr-Gln-Arg-Leu-Ala-Glu-Phe-Leu-Arg-His-Ser-Ser-Asn-Asn-Phe-Gly-Pro-Ile-Leu-Pro-Pro-Thr-Asn-Val-Gly-Ser-Asn-Thr-Pro-NH₂ (Disulfide bridge: Cys³-Cys⁸)
Sequence (Semaglutide): His-[Aib]-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-[C18 diacid-γ-Glu-(AEEA)₂-Lys]-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly
Purity: ≥ 99%
Form: Lyophilized powder
Storage: Store at ≤ -20°C in a cool, dry place, protected from light and moisture
Solubility: Soluble in sterile water and DMSO; prepare working solutions per laboratory protocol