Insulin Degludec (LYS) is an ultra-long-acting basal insulin analogue engineered for stable, once-daily blood glucose control in both type 1 and type 2 diabetes. The (LYS) designation refers to its specific modification at lysine B29, acylated with a glutamyl spacer and a C16 fatty acid (hexadecanoic acid), facilitating multi-hexamer formation in subcutaneous tissue and slow monomer release into the bloodstream. This design underpins its prolonged action and reduced risk of hypoglycemia.
Appearance
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Clear, colorless solution for subcutaneous injection.
Source
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Produced by recombinant DNA technology in yeast (Saccharomyces cerevisiae), followed by chemical modification and purification for pharmaceutical use.
Molecular Weight and Structure
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Molecular weight >5.8 kDa due to di-heptadecanoyl modification.
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Modified at lysine B29 with a glutamyl spacer and C16 fatty acid, enabling multi-hexamer depot formation for controlled release.
Biological Activity
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Lowers blood glucose by enhancing cell uptake and suppressing hepatic production.
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Binds insulin receptor to activate signaling pathways.
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The lysine modification supports extended dosing intervals and reduced hypoglycemia risk.
Purity & Microbial Contamination
| Attribute | Specification |
|---|---|
| Purity | ≥95% by High-Performance Liquid Chromatography (HPLC) |
| Sterility | Must meet pharmacopeial and regulatory standards |
| Endotoxin | Tested using Limulus Amebocyte Lysate (LAL) assay |
| Bioburden | Controlled and validated in pharmaceutical use |
Identity & Quality Control
| Attribute | Specification |
|---|---|
| Mass Spectrometry (MS) | Confirms molecular weight and LysB29 acylation modification |
| Peptide Mapping | Verifies amino acid sequence and exact modification site |
| Amino Acid Analysis | Confirms correct amino acid composition |
| HPLC | Evaluates purity and detects aggregates |
| Aggregation Analysis | Monitors physical stability/formulation (e.g., hexamer/multi-hexamer formation) |
| Bioactivity Assays | Tests insulin receptor binding and glucose-lowering activity |
Shelf Life and Storage
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Typically 2–3 years if stored refrigerated at 2–8°C, protected from light, and never frozen. Follow manufacturer’s instructions after opening.
Application
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Treatment for type 1 and type 2 diabetes mellitus; once-daily administration.
Key Characteristics
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Human insulin analogue with unique lysine B29 acylation.
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Ultra-long action via multi-hexamer subcutaneous formation.
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Reduced risk of hypoglycemia versus short-acting basal insulins.
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Sterile solution for injection.
Citation
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Structural and dynamic features of cagrilintide binding to receptors
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Cagrilintide lowers bodyweight through brain amylin receptor interaction
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Comparing efficacies of dual amylin and calcitonin receptor agonists
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Weekly Somapacitan efficacy and tolerance in children with GH deficiency
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Mechanisms and regulation of glucagon-like peptide-1 receptor

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