Cagrilintide/Semaglutide Blend 5+5mg

Compound Name: Cagrilintide + Semaglutide blend

Synonyms: CagriSema, Cagrilintide/Semaglutide blend, Amylin analogue + GLP-1RA combination CAS Number:

• Cagrilintide: 1415456-99-3
• Semaglutide: 910463-68-2

Molecular Formula:

• Cagrilintide: C₁₉₄H₃₁₂N₅₄O₅₉S₂
• Semaglutide: C₁₈₇H₂₉₁N₄₅O₅₉

Molecular Weight:

• Cagrilintide: 4409 g/mol
• Semaglutide: 4113.4 g/mol

Structure: Cagrilintide: Amylin analogue; Semaglutide: Linear polypeptide

Peptide Sequence:

• Cagrilintide: γGlu-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
• Semaglutide: H-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH

Chemical Structure:

Cagrilintide:                                                                 Semaglutide:

Source: PubChem                                                      Source: PubChem

Mechanism of Action: Cagrilintide acts primarily as a long-acting amylin analogue, stimulating amylin and calcitonin receptors to promote satiety, slow gastric emptying, and suppress postprandial glucagon release. Semaglutide is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion, suppresses appetite via central nervous system pathways, and delays gastric emptying. When administered together, their mechanisms converge to amplify appetite regulation, energy intake reduction, and glycemic improvements, exceeding the individual effects of monotherapy by acting on complementary neuroendocrine circuits regulating body weight and metabolism^1-3.

Biological Activity: Cagrilintide and semaglutide, when co-administered, produce synergistic reductions in bodyweight (up to ~15–17% over 20–32 weeks in clinical trials) and significant improvements in glycemic parameters, including HbA1c and fasting glucose. Their effects are marked by increased satiety, reduced appetite, and improved metabolic biomarkers, with a safety profile dominated by mild to moderate gastrointestinal adverse events.^1-3.

Storage: Store at –20°C or lower, protected from light, as a lyophilized/frozen peptide blend until reconstitution. After reconstitution, store at 2–8°C and use within 7 days.

Drug Categories: Anti-obesity agents, Antidiabetic agents, Peptide therapeutics, Amylin analogues, GLP-1 receptor agonists

Additional Notes: For investigational use in laboratory settings only.

Summary Table:

Disclaimer: For Research Use Only. Not intended for human or veterinary use. This compound is supplied solely for laboratory and R&D purposes.

Detailed Product Description

The cagrilintide and semaglutide combination is a next-generation investigational peptide blend developed to maximize weight loss and metabolic control. Cagrilintide is a long-acting amylin analogue with dual amylin and calcitonin receptor activity, whereas semaglutide is a once-weekly GLP-1 receptor agonist with robust anti-hyperglycemic and appetite-suppressing effects. Preclinical and clinical studies demonstrate that co-administration of these peptides achieves superior reductions in bodyweight, appetite, and fasting glucose than either agent alone—achieving up to a 17% reduction in bodyweight in non-diabetic individuals and a 15.6% reduction in patients with type 2 diabetes over 20–32 weeks. Notably, this combination exerts additive or synergistic actions by targeting distinct neuroendocrine pathways: cagrilintide modulates homeostatic and hedonic food regulation centers in the hindbrain and hypothalamus, while semaglutide engages central and peripheral GLP-1 pathways to reduce calorie intake and improve glycemic regulation. The blend is well tolerated, with gastrointestinal effects being the most frequent adverse events and no evidence of clinically significant safety concerns or neutralizing antibody responses to cagrilintide during short-term exposure^1-3.

Research Highlights

• Co-administration shows markedly greater bodyweight reduction than either monotherapy¹.
• Synergistic effects on appetite suppression and satiety^1-3.
• Improves glycemic control (HbA1c, fasting plasma glucose) in overweight/obese and type 2 diabetic populations².
• Favorable safety and tolerability profile in phase 1b and 2 trials (mainly mild/moderate GI events)¹.
• No significant pharmacokinetic interaction observed between cagrilintide and semaglutide^1-3.

Mechanism of Action

The combination of cagrilintide and semaglutide exploits complementary mechanisms to induce additive or synergistic metabolic, glycemic, and appetite-suppressing effects, bridging the efficacy gap between pharmacotherapy and surgical approaches in obesity management.

Amylin/Calcitonin Receptor Agonism (cagrilintide)

• Delays gastric emptying, reduces postprandial glucagon, and strongly promotes satiety
• Modulates appetite-regulating centers in the hindbrain, hypothalamus, and brain reward circuits, directly influencing food intake and choice
• May transiently activate the renin-angiotensin-aldosterone system with dose escalation, but without blood pressure or electrolyte derangements

GLP-1 Receptor Agonism (semaglutide)

• Stimulates glucose-dependent insulin secretion and suppresses glucagon release to improve glycemic control
• Reduces appetite and ad libitum energy intake, with central effects on GLP-1R-expressing nuclei in hypothalamus and brainstem
• Delays gastric emptying and increases satiety, contributing to progressive bodyweight loss

Pharmacokinetic Profile

• Route of Administration: Subcutaneous Injection
• Dosing Frequency: Once weekly
• Half-life: Cagrilintide: 7-8 days; Semaglutide: 6-7 days

Formulation & Handling

• Store at –20°C or lower, protected from light, as a lyophilized/frozen peptide blend until reconstitution.
• After reconstitution, store at 2–8°C and use within 7 days.

Selected Clinical Trial Activity

References

¹Enebo, L. B. et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet 397, 1736–1748 (2021).

²Frias, J. P. et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet 402, 720–730 (2023).

³Goldenberg, R. M. et al. Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high-dose GLP-1 receptor agonists and GLP-1 receptor-based co-agonists. Obesity Reviews 25, e13663 (2024).