The hypoglycemic action of glyburide is due to stimulation of pancreatic islet cells, which results in an increase in insulin secretion. Sulfonylureas are believed to bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, thereby reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin. The drug is not effective in the absence of functioning beta-cells, as occurs in diabetes mellitus type 1, or when the number of viable beta-cells is low, as occurs in severe cases of diabetes mellitus type 2.
Prolonged administration of glyburide also produces extrapancreatic effects that contribute to its hypoglycemic activity. These effects include reduction of basal hepatic glucose production and an enhanced peripheral sensitivity to insulin secondary to an increase in insulin receptors or to changes in the events that follow insulin-receptor binding. The relative importance of each of these actions to the overall therapeutic effect of the drug will vary among oral antidiabetic agents and from patient to patient, which may account for the variability in potency among these drugs. Like glipizide, glyburide exhibits mild diuretic actions but does not affect uric acid concentrations.