Insulin Glulisine

nsulin glulisine is a rapid-acting insulin analogue used to improve glycemic control in type 1 and type 2 diabetes mellitus. It mimics endogenous insulin by promoting glucose uptake into muscle, fat, and liver cells, suppressing hepatic glucose production, and regulating carbohydrate, fat, and protein metabolism. Structural amino acid modifications reduce hexamer formation, allowing faster absorption, with an onset of action within 15 minutes, a peak effect at 30–90 minutes, and a duration of approximately 5 hours. As a bolus (mealtime) insulin, insulin glulisine is commonly used in combination with long-acting basal insulin to mimic physiological insulin secretion and maintain stable blood glucose levels while reducing the risk of diabetes-related complications.

Insulin glulisine is a short-acting form of insulin used for glycemic control in type 1 and type 2 diabetes mellitus.

Insulin glulisine is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.

• Diabetes Mellitus
• Type 1 Diabetes Mellitus
• Hyperglycemia during critical illness

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.

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.

In a study in patients with type 1 diabetes (n=20) after subcutaneous administration of 0.15 units/kg, the median time to maximum concentration (Tmax) was 60 minutes (range 40 to 120 minutes) and the peak concentration (Cmax) was 83 microunits/mL (range 40 to 131 microunits/mL) for insulin glulisine compared to a median Tmax of 120 minutes (range 60 to 239 minutes) and a Cmax of 50 microunits/mL (range 35 to 71 microunits/mL) for regular human insulin. When insulin glulisine was injected subcutaneously into different areas of the body, the time-concentration profiles were similar. The absolute bioavailability of insulin glulisine after subcutaneous administration is approximately 70%, regardless of injection area (abdomen 73%, deltoid 71%, thigh 68%).

13 L

Elimination half life= 42 minutes (following subcutaneous injection)

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.

• Avoid alcohol. Alcohol may impair blood glucose control.

• Inject within 15 minutes before a meal or within 20 minutes after starting a meal into the abdomen, thigh, or upper arm.
• Rotate injection sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis.
• Should generally be used in regimens with intermediate or long-acting insulin.

• Administer by continuous subcutaneous infusion using an insulin pump in a region recommended in the instructions from the pump manufacturer.
• Rotate infusion sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis.
• Do not dilute or mix insulins in external insulin pumps.