Insulin Glargine

160337-95-1 Categories: , ,
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Product Details:

  • Product Name: Insulin Glargine
  • CAS #: 160337-95-1
  • Mode of Action:

    Insulin glargine binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism. Insulin glargine is completely soluble at pH 4, the pH of administered solution, and has low solubility at physiological pH 7.4. Upon subcuteous injection, the solution is neutralized resulting in the formation of microprecipitates. Small amounts of insulin glargine are released from microprecipitates giving the drug a relatively constant concentration over time profile over 24 hours with no pronounced peak. This release mechanism allows the drug to mimic basal insulin levels within the body.

  • Pharmacodynamics:

    Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin glargine is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals. The onset of action of insulin glargine is approximately 90 minutes and its duration of action is up to 24 hours. The action profile of insulin glargine is peakless. The significance of this finding is that insulin glargine has a lower chance of nocturnal hypoglycemia.

  • Metabolism:

    Partly metabolized to two active metabolites with similar in vitro activity to insulin: A21-Gly-insulin and A21-Gly-des-B30-Thr-insulin.

  • Toxicity:

    Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. Other adverse events that may occur include allergic reaction, injection site reaction, lipodystrophy, pruritis, and rash.

  • IUPAC: 21(sup A)-glycine-30(supp B)a-L-arginine-30(supp B)b-L-arginineinsulin (human)
  • ATC: A10AE04
  • DrugBank: DB00047 (BIOD00045, BTD00045, DB01308)
  • Formula: C267-H404-N72-O78-S6
  • Molecular Mass: 6062.9506
  • Synonyms: 21(sup A)-Glycine-30(sup B)a-L-arginine-30(sup B)b-L-arginine insulin (human), A21-Gly-B31-Arg-B32-Arg-insulin, Glargine, HOE 71GT, HOE 901, Insulin (human), 21(sup A)-glycine-30(sup B)a-L-arginine-30(sup B)b-L-arginine-, Insulin glargine, Insulin, glycyl(A21)-arginyl(B31,B32)-, Lantus, Lantus R, Lantus Solostar, LY 2963016, Optisulin, SoloStar, SoloStar [Insulin delivery pen], Toujeo, UNII-2ZM8CX04RZ
  • AHFS Code: 08:20.1
  • General Reference:


    1. Chatterjee S, Tringham JR, Davies MJ: Insulin glargine and its place in the treatment of Types 1 and 2 diabetes mellitus. Expert Opin Pharmacother. 2006 Jul;7(10):1357-71. Pubmed
    2. Dunn CJ, Plosker GL, Keating GM, McKeage K, Scott LJ: Insulin glargine: an updated review of its use in the management of diabetes mellitus. Drugs. 2003;63(16):1743-78. Pubmed
    3. Home PD, Ashwell SG: An overview of insulin glargine. Diabetes Metab Res Rev. 2002 Sep-Oct;18 Suppl 3:S57-63. Pubmed
    4. Jones R: Insulin glargine (Aventis Pharma). IDrugs. 2000 Sep;3(9):1081-7. Pubmed
    5. Wang F, Carabino JM, Vergara CM: Insulin glargine: a systematic review of a long-acting insulin analogue. Clin Ther. 2003 Jun;25(6):1541-77, discussion 1539-40. Pubmed
    6. Warren E, Weatherley-Jones E, Chilcott J, Beverley C: Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine. Health Technol Assess. 2004 Nov;8(45):iii, 1-57. Pubmed
    7. Owens DR, Bolli GB: Beyond the era of NPH insulin—long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application. Diabetes Technol Ther. 2008 Oct;10(5):333-49. doi: 10.1089/dia.2008.0023. Pubmed


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