Basagine Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: The primary activity of insulin glargine is the regulation of glucose metabolism. It inhibits hepatic glucose production and lowers blood glucose level by enhancing peripheral glucose uptake especially by skeletal muscle and fat. It also inhibits lipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis. Insulin Glargine is a human insulin analogue designed to have a low solubility at neutral pH. It is completely soluble at the acidic pH of the injection solution (pH 4). After injection into the subcutaneous tissue, the acidic solution is neutralized leading to formation of micro-precipitates from which small amounts of insulin glargine are continuously released, providing a smooth, peakless, predictable concentration/time profile with a prolonged duration of action.
Pharmacokinetics: Absorption and Bioavailability: Following subcutaneous injection, absorption of insulin glargine is slower and more prolonged compared with that of isophane (NPH) human insulin; the serum concentration-time profile for insulin glargine is relatively constant over 24 hours. After subcutaneous injection of 0.3 units/kg insulin glargine in patients with type 1 diabetes, a relatively constant concentration/time profile has been demonstrated. The duration of action after abdominal, deltoid, or thigh subcutaneous administration is almost similar.
Insulin glargine injected once daily will reach steady state levels in 2-4 days after first dose.
Metabolism: Insulin glargine is partly metabolized in the subcutaneous depot at the carboxyl terminus of the B-Chain to form the active metabolites i.e. M1 (21^A-Gly-insulin and M2 (21^A-Gly-des-30^B-Thr-insulin) having similar in vitro activity to insulin.
Special Population: Age, Race and Gender: Age, race and gender did not show difference in safety and efficacy between insulin glargine and NPH human insulin.
Renal & Hepatic Insufficiency: The effect of the renal & hepatic insufficiency on the pharmacokinetics of Insulin Glargine rDNA origin has not been studied. However, some studies with human insulin have shown increased circulating levels of insulin in patients with renal & hepatic failure. Careful glucose monitoring and dose adjustments may be necessary in patients with renal & hepatic dysfunction.