Glyburide

• Type 2 Diabetes Mellitus
• Blood Sugar Control
• Sulfonylurea Therapy
• Oral Antidiabetic Treatment

Glyburide (also known as glibenclamide) is a second-generation sulfonylurea used for the management of type 2 diabetes mellitus. This oral medication stimulates insulin release from pancreatic beta cells and has been widely used for decades as an effective glucose-lowering agent.

Mechanism of Action

Glyburide stimulates insulin secretion from functional pancreatic beta cells by binding to the sulfonylurea receptor-1 (SUR1) subunit of the ATP-sensitive potassium (KATP) channel on the beta cell membrane. This binding closes the KATP channel, causing membrane depolarization, opening of voltage-dependent calcium channels, calcium influx, and subsequent insulin release. Glyburide also has extrapancreatic effects that may contribute to its glucose-lowering action, including reduction of hepatic glucose production and enhancement of peripheral glucose uptake. The medication has a relatively long duration of action, increasing the risk of prolonged hypoglycemia compared to some other sulfonylureas.

Available Formulations

Glyburide is available in two formulations: regular tablets (1.25 mg, 2.5 mg, 5 mg) and micronized tablets (1.5 mg, 3 mg, 4.5 mg, 6 mg). The micronized formulation has enhanced bioavailability and is not equivalent to the regular tablets on a milligram-per-milligram basis. Generic formulations are available for both.

Medical Uses

Glyburide is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It can be used as monotherapy or in combination with metformin or insulin. Glyburide has historically been used for gestational diabetes in some settings, though this use is controversial due to placental transfer and neonatal hypoglycemia concerns.

Dosing Guidelines

For regular tablets, the initial dose is 2.5-5 mg daily with breakfast or the first main meal; maintenance range is 1.25-20 mg daily (maximum 20 mg). For micronized tablets, initial dose is 1.5-3 mg daily; maintenance range is 0.75-12 mg daily (maximum 12 mg). Doses of 10 mg (regular) or 6 mg (micronized) or more should be divided twice daily. Elderly patients or those with renal/hepatic impairment should start at lower doses.

Important Safety Information

Glyburide causes hypoglycemia, which can be prolonged and severe, particularly in elderly patients, those with renal or hepatic impairment, and with irregular eating or alcohol use. The relatively long duration of action increases hypoglycemia risk compared to shorter-acting agents. Sulfonylureas carry a warning for potential increased cardiovascular mortality based on the UGDP study. Glyburide is not recommended in patients with G6PD deficiency due to hemolytic anemia risk. Secondary failure (loss of efficacy) may occur over time.

Drug Interactions

Many drugs can increase hypoglycemic effect: NSAIDs, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, MAO inhibitors, beta-blockers, fluconazole, and other antidiabetic agents. Drugs that may reduce effectiveness: thiazides, other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, phenytoin, nicotinic acid, sympathomimetics, and calcium channel blockers. Bosentan may increase liver enzymes and decrease glyburide levels; concurrent use is contraindicated.

Special Populations

Glyburide is not recommended during pregnancy; it crosses the placenta and may cause neonatal hypoglycemia. Insulin is preferred for diabetes during pregnancy. Glyburide may be present in breast milk; caution is advised. Safety and efficacy have not been established in pediatric patients. Elderly patients are at higher risk for hypoglycemia and should use with caution; starting at lower doses is recommended. Use with caution in renal impairment (risk of accumulation and prolonged hypoglycemia); some sources recommend avoiding when CrCl is less than 50 mL/min. Use with caution in hepatic impairment; reduced metabolism may increase hypoglycemia risk.