indication

For concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.

pharmacology

Glimepiride, like glyburide and glipizide, is a "second-generation" sulfonylurea agents. Glimepiride is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin.

mechanism of action

The mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glimepiride likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin.

toxicity

Severe hypoglycemic reactions with coma, seizure, or other neurological impairment.

biotransformation

Hepatic. Following either an intravenous or oral dose, glimepiride is completely metabolized by oxidative biotransformation to a major metabolite, cyclohexyl hydroxymethyl derivative (M1), via the hepatic cytochrome P450 II C9 subsystem. M1 is further metabolized to the carboxyl derivative (M2) by one or several cytosolic enzymes. M1, but not M2, possessed approximately one third of the pharmacologic activity of its parent in an animal model. However, whether the glucose-lowering effect of M1 is clinically significant is not clear.

absorption

Completely (100%) absorbed following oral administration.

half life

Approximately 5 hours following single dose.

drug interactions

Cyclosporine: The sulfonylurea, glimepiride, may increase the effect of cyclosporine.

Gemfibrozil: Gemfibrozil increases the effect and toxicity of rosiglitazone/pioglitazone

Glucosamine: Possible hyperglycemia

Ketoconazole: Ketoconazole increases the effect of rosiglitazone

Rifampin: Rifampin may decrease the effect of sulfonylurea, glimepiride.

Somatropin recombinant: Somatropin may antagonize the hypoglycemic effect of glimepiride. Monitor for changes in fasting and postprandial blood sugars.

Tolbutamide: Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Glimepiride. Consider alternate therapy or monitor for changes in Glimepiride therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.