Introduction
Glyburide (also known as glibenclamide) is a second-generation sulfonylurea oral antidiabetic agent used in the management of type 2 diabetes mellitus. First approved by the FDA in 1984, it remains one of the most commonly prescribed medications for glycemic control. As an insulin secretagogue, glyburide stimulates pancreatic beta cells to release insulin, helping to lower blood glucose levels in patients with preserved pancreatic function.
Mechanism of Action
Glyburide exerts its hypoglycemic effect primarily by binding to ATP-sensitive potassium channels on pancreatic beta cells. This binding causes depolarization of the cell membrane, opening voltage-dependent calcium channels, and resulting in calcium influx that triggers insulin exocytosis. The drug requires functional beta cells to produce its therapeutic effect. Additionally, glyburide may enhance peripheral tissue sensitivity to insulin and reduce hepatic glucose production, though these effects are secondary to its primary insulin-secreting action.
Indications
Glyburide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It may be used as monotherapy or in combination with other oral antidiabetic agents including metformin or thiazolidinediones when glycemic control is not achieved with single-agent therapy. Glyburide is not indicated for type 1 diabetes mellitus or diabetic ketoacidosis.
Dosage and Administration
Initial dose: 2.5-5 mg once daily with breakfast or first main meal Maintenance dose: 1.25-20 mg daily, given as single or divided doses Maximum dose: 20 mg daily Dosage adjustments:- Elderly patients: Initiate with 1.25-2.5 mg daily
- Renal impairment: Use with caution; not recommended in severe impairment (eGFR <30 mL/min)
- Hepatic impairment: Initiate with lower doses and monitor closely
Take with meals to minimize gastrointestinal upset and reduce hypoglycemia risk. Dose titration should occur at weekly intervals based on glycemic response.
Pharmacokinetics
Absorption: Well absorbed from GI tract (90-100% bioavailability); food may slightly delay but not reduce overall absorption Distribution: Highly protein-bound (>99%), primarily to albumin; volume of distribution approximately 0.2 L/kg Metabolism: Extensively metabolized hepatically via CYP2C9 and CYP3A4 to inactive metabolites Elimination: Half-life 4-10 hours; excreted equally in urine (50%) and feces (50%) as metabolites Onset: 2-4 hours; Peak effect: 4-8 hours; Duration: Up to 24 hoursContraindications
- Hypersensitivity to glyburide or other sulfonylureas/sulfonamides
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal or hepatic impairment
- Pregnancy (Category C; not recommended due to potential hypoglycemia in neonates)
- Concomitant use with bosentan
Warnings and Precautions
Hypoglycemia: Risk increased with renal/hepatic impairment, elderly patients, malnutrition, adrenal/pituitary insufficiency, and alcohol consumption Cardiovascular mortality: Increased cardiovascular mortality reported with other sulfonylureas Hemolytic anemia: Possible in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Syndrome of inappropriate antidiuretic hormone (SIADH): Water retention and hyponatremia reported Hepatic porphyria: May exacerbate acute porphyria Secondary failure: Diminished efficacy over time may occur Stress situations: May require temporary discontinuation during major surgery, illness, or traumaDrug Interactions
Increased hypoglycemia risk with:- Insulin and other antidiabetic agents
- Beta-blockers (may mask hypoglycemia symptoms)
- Alcohol
- ACE inhibitors
- Fluconazole, sulfonamides, warfarin (CYP2C9 inhibitors)
- MAO inhibitors, salicylates
- Thiazide diuretics
- Corticosteroids
- Phenytoin
- Estrogens, oral contraceptives
- Isoniazid
- Sympathomimetics
- Thyroid products
- Calcium channel blockers
- Rifampin (CYP2C9 inducer)
Adverse Effects
Common (≥1%):- Hypoglycemia (4-33%)
- Nausea (2-5%)
- Upper respiratory infection (2-5%)
- Headache (2-5%)
- Dyspepsia (1-3%)
- Severe hypoglycemia requiring intervention
- Hemolytic anemia
- Hepatitis, cholestatic jaundice
- Syndrome of inappropriate antidiuretic hormone (SIADH)
- Stevens-Johnson syndrome
- Thrombocytopenia, leukopenia, agranulocytosis
- Photosensitivity reactions
- Hyponatremia
Monitoring Parameters
Before initiation:- HbA1c, fasting glucose
- Renal function (serum creatinine, eGFR)
- Hepatic function (ALT, AST, bilirubin)
- Complete blood count
- Blood glucose monitoring (fasting and postprandial)
- HbA1c every 3-6 months
- Signs/symptoms of hypoglycemia
- Weight changes
- Hepatic and renal function annually or as clinically indicated
- Periodic CBC in patients with hematologic disorders
Patient Education
- Take medication with meals as directed
- Recognize symptoms of hypoglycemia (sweating, tremor, hunger, confusion)
- Carry glucose tablets or quick-acting sugar source
- Wear medical identification indicating diabetes diagnosis
- Avoid excessive alcohol consumption
- Do not skip meals while taking glyburide
- Report any unusual symptoms, dark urine, or yellowing of skin/eyes
- Understand that glycemic control requires comprehensive approach including diet, exercise, and weight management
- Regular blood glucose monitoring is essential
- Inform all healthcare providers about glyburide use before any procedures
References
1. American Diabetes Association. (2023). Standards of Medical Care in Diabetes. Diabetes Care. 46(Supplement 1):S1-S291. 2. Glyburide prescribing information. FDA approved label. 3. Bennett WL, et al. (2011). Comparative effectiveness and safety of medications for type 2 diabetes. Annals of Internal Medicine. 154(9):602-613. 4. Inzucchi SE, et al. (2015). Management of hyperglycemia in type 2 diabetes. Diabetes Care. 38(1):140-149. 5. Lexicomp Online. (2023). Glyburide monograph. 6. UK Prospective Diabetes Study (UKPDS) Group. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet. 352(9131):837-853. 7. Nathan DM, et al. (2009). Medical management of hyperglycemia in type 2 diabetes. Diabetes Care. 32(1):193-203.