indication

For use as an adjunct to diet for the control of hyperglycemia and its associated symptomatology in patients with non-insulin-dependent diabetes mellitus (NIDDM; type II), formerly known as maturity-onset diabetes, after an adequate trial of dietary therapy has proved unsatisfactory.

pharmacology

Glipizide, a second-generation sulfonylurea, is used with diet to lower blood glucose in patients with diabetes mellitus type II. The primary mode of action of glipizide in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. In humans glipizide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. In man, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. Some patients fail to respond initially, or gradually lose their responsiveness to sulfonylurea drugs, including glipizide.

mechanism of action

Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, 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.

toxicity

The acute oral toxicity was extremely low in all species tested (LD50 greater than 4 g/kg). Overdosage of sulfonylureas including glipizide can produce hypoglycemia.

biotransformation

Hepatic. The major metabolites of glipizide are products of aromatic hydroxylation and have no hypoglycemic activity. A minor metabolite which accounts for less than 2% of a dose, an acetylaminoethyl benzine derivatives, is reported to have 1/10 to 1/3 as much hypoglycemic activity as the parent compound.

absorption

Gastrointestinal absorption is uniform, rapid, and essentially complete.

half life

2-5 hours

route of elimination

The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine.

drug interactions

Acebutolol: Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.

Acetylsalicylic acid: Acetylsalicylic acid increases the effect of the sulfonylurea, glipizide.

Atenolol: The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.

Bisoprolol: The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.

Carvedilol: The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.

Chloramphenicol: Chloramphenicol may increase the effect of sulfonylurea, glipizide.

Clofibrate: Clofibrate may increase the effect of sulfonylurea, glipizide.

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

Esmolol: The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.

Labetalol: The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.

Metoprolol: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Nadolol: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Oxprenolol: The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.

Phenylbutazone: Phenylbutazone increases the effect of the hypoglycemic agent

Pindolol: The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.

Propranolol: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

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

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

Timolol: The beta-blocker, timolol, may decrease symptoms of hypoglycemia.

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