Insulin Glulisine

Status : approved

Category

Antidiabetic Agents

Therapeutic Classification

INSULINS AND ANALOGUES

ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
INSULINS AND ANALOGUES

Description

Insulin glulisine is a biosynthetic, rapid-acting human insulin analogue produced in a non-pathogenic laboratory strain of _Escherichia coli_ (K12). This recombinant hormone differs from native human insulin in that the amino acid arginine at position B3 is replaced by lysine and the lysine at position B29 is replaced by glutamic acid. These structural modifications decrease hexamer formation, stabilize insulin glulisine monomers and increase the rate of absorption and onset of action compared to human insulin.

Used

For the treatment of Type 1 and 2 diabetes mellitus. Should be used in regimens including a long-acting or basal insulin analogue unless it is used in a continuous infusion pump. May be used with oral antidiabetic agents.

Mechanism Of Action

Insulin glulisine 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 and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the arginine at position B3 for lysine and replacement of the B29 lysine with glutamic acid decreases the propensity to form hexamers, stabilizes the hormone in monomeric form and results in a rapid rate of absorption and short duration of action.

Dosage

Form Route Strength
Injection, solution subcutaneous 100 [iU]/mL
Solution subcutaneous 100 unit

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. Postprandial insulin spikes are 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 glulisine is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin glulisine is approximately 15 minutes. Its activity peaks 60 minutes following subcutaneous injection and its duration of action is 2-4 hours.

Toxic Effect

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.

Absorption

Compared to regular human insulin, insulin glulisine is faster absorbed. When 0.15 units/kg was subcutaneously administered to type 1 diabetes patients, the pharmacokinetic parameters are as follows: Tmax = 60 minutes (range of 40 – 120 minutes); Cmax = 83 microUnits/mL (range of 40 – 131 microUnits/mL). Absolute bioavailability following subcutaneous administration is approximately 70%, regardless of site of injection.

Half Life

Elimination half life= 42 minutes (following subcutaneous injection)

Volume of Distribution

13 L

Chemical Classification

Peptides

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

Brands

name Dosage form Country
Apidra injection, solution US
Apidra (10ml Vial) solution Canada
Apidra (3ml Cartridge) solution Canada
Apidra (3ml Optiset Presentation) solution Canada
Apidra (3ml Solostar Disposable Prefilled Pen) solution Canada
Apidra Solostar injection, solution US

Drug Drug Interactions

  •  Acetohexamide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Acetylsalicylic acid  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Alogliptin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Aripiprazole  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Arsenic trioxide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Articaine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Asenapine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Atazanavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Bendroflumethiazide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Betamethasone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Brexpiprazole  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Bumetanide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Buserelin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Canagliflozin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Ceritinib  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Chlorothiazide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Chlorpropamide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Chlorthalidone  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Clozapine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Corticotropin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Cortisone acetate  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Cyproterone acetate  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Dabrafenib  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Danazol  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Darunavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Desogestrel  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Dexamethasone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Diazoxide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Dienogest  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Dihydrotestosterone  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Disopyramide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Drospirenone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Edetic Acid  : May enhance the hypoglycemic effect of Insulin.
  •  Edetic Acid  : May enhance the hypoglycemic effect of Insulin.
  •  Epinephrine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Estradiol  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Estropipate  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Ethacrynic acid  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Ethinyl Estradiol  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Ethynodiol  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Etonogestrel  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Everolimus  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Fludrocortisone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Fosamprenavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Furosemide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Gliclazide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Glimepiride  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Glipizide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Gliquidone  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Glyburide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Goserelin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Histrelin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Hydrochlorothiazide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Hydrocortisone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Hydroxyprogesterone caproate  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Iloperidone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Indapamide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Indinavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  inhaled insulin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Aspart  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Detemir  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Glargine  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Lispro  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Regular  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin, isophane  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Lanreotide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Leuprolide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Levonorgestrel  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Linagliptin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Lipoic Acid  : May enhance the hypoglycemic effect of Antidiabetic Agents.
  •  Liraglutide  : May enhance the hypoglycemic effect of Insulin.
  •  Lopinavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Lurasidone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Mecasermin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Medroxyprogesterone Acetate  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Megestrol acetate  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Mestranol  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Metformin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Methotrimeprazine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Methyclothiazide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Methylprednisolone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Metolazone  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Metreleptin  : May enhance the hypoglycemic effect of Insulin.
  •  Mifepristone  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Nateglinide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Nelfinavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Niacin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Nilotinib  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Norethindrone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Norgestimate  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Octreotide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Olanzapine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Oxandrolone  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Paliperidone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Pasireotide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Pegvisomant  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Pentamidine  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Pioglitazone  : May enhance the adverse/toxic effect of Insulin. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination.
  •  Piperazine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Pipotiazine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Pramlintide  : May enhance the hypoglycemic effect of Insulin.
  •  Prednisolone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Prednisone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Progesterone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Quetiapine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Quinine  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Repaglinide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Risperidone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Ritonavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Rosiglitazone  : Insulin may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination.
  •  Salicylate-sodium  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Saquinavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Saxagliptin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Sirolimus  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Sulfadiazine  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Sulfamethoxazole  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Sulfisoxazole  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Sunitinib  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Tacrolimus  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Temsirolimus  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Testosterone  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Tipranavir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Tolazamide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Tolbutamide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Torasemide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Triamcinolone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Triptorelin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Vildagliptin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Vorinostat  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Ziprasidone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.

Calculated Property

kind Value Source

Affected organism

Humans and other mammals

Target within organism

  • Insulin receptor : in Human