Pharmacology: Pharmacodynamics: The primary activity of Insulin, including Insulin Glargine, is regulation of glucose metabolism. Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis. Insulin Glargine differs from other Insulins because its unique structure provides a smooth and peakless profile with a prolonged duration of action of 24 hours (end of observation period) compared to 14.5 hours for NPH human Insulin. In clinical studies, intravenous Insulin Glargine and human Insulin have been shown to be equipotent when given at the same doses. The onset of action of Insulin Glargine is slower than NPH human Insulin. The effect profile of Insulin Glargine is smooth and peakless, and the duration of its effect is prolonged compared to NPH human Insulin.
Pharmacokinetics: After subcutaneous injection of Insulin Glargine, the Insulin serum concentrations indicate a slower, more prolonged absorption and a lack of a peak in comparison to NPH human Insulin. Concentrations are thus consistent with the time profile of the pharmacodynamic activity of Insulin Glargine. Insulin Glargine is a human Insulin analogue that has been designed to have low solubility at neutral pH. At pH 4, the pH of the Insulin Glargine injection solution, it is completely soluble. After injection into the subcutaneous tissue, the acidic solution is neutralised, leading to formation of micro precipitates from which small amounts of Insulin Glargine are continuously released, providing a smooth, peakless, predictable time/concentration profile and a prolonged duration of action. This allows once daily dosing to meet a patient's basal Insulin needs. Insulin Glargine is partly degraded in the subcutaneous depot at the carboxyl terminus of the B chain to form the active metabolites, with similar in vitro activity to Insulin.