Glibenclamide

FDA-Approved Indications:

• Type 2 Diabetes Mellitus (T2DM):
  As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

Clinically Accepted Off-Label Uses:

• Gestational Diabetes Mellitus (GDM): Sometimes used as an alternative to insulin, although insulin is preferred; careful monitoring is required.
• Combination Therapy: May be used in combination with metformin or insulin for patients inadequately controlled on monotherapy.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Adults (Type 2 Diabetes Mellitus):

• Initial dose: 2.5 mg once daily, taken with breakfast or first main meal.
• Titrate by 2.5 mg at weekly intervals depending on glycemic response.
• Maintenance dose: 2.5–10 mg daily (single or divided dose).
• Maximum dose: 20 mg per day.

Elderly or Debilitated Patients:

• Start with 1.25–2.5 mg once daily to minimize hypoglycemia.

Renal or Hepatic Impairment:

• Lower doses required.
• Avoid use in severe impairment due to risk of prolonged hypoglycemia.

Pediatric Use:

• Safety and efficacy not established; not recommended.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Glibenclamide is a second-generation sulfonylurea.

• It binds to sulfonylurea receptors (SUR1) on pancreatic β-cells.
• This causes closure of ATP-sensitive potassium channels, leading to depolarization.
• Calcium influx triggers insulin release from β-cells.
• The increased insulin lowers blood glucose by enhancing glucose uptake and utilization.

• Absorption: Well absorbed orally; peak plasma concentration within 2–4 hours.
• Distribution: Highly protein-bound (~99%).
• Metabolism: Extensively metabolized in the liver (CYP3A4, CYP2C9).
• Excretion: Primarily via bile (metabolites) and partly in urine.
• Half-life: 4–10 hours, but hypoglycemic effect may last up to 24 hours.

• Pregnancy: FDA Pregnancy Category C. Insulin is preferred for diabetes management during pregnancy; glibenclamide may cross the placenta in small amounts.
• Lactation: Not recommended; drug and/or metabolites may pass into breast milk and cause hypoglycemia in infants.

• Antidiabetic agent – Sulfonylurea (2nd generation).

• Hypersensitivity to sulfonylureas or sulfonamides.
• Type 1 diabetes mellitus.
• Diabetic ketoacidosis (DKA) with or without coma.
• Severe renal or hepatic impairment.
• Pregnancy and lactation (relative contraindication).

• Hypoglycemia risk is significant, especially in elderly, malnourished, or renally impaired patients.
• Use with caution in patients with adrenal, pituitary insufficiency, or thyroid disorders.
• May cause secondary failure over time as pancreatic β-cell function declines.
• Avoid alcohol – may potentiate hypoglycemia.
• Regular blood glucose and HbA1c monitoring required.

Common:

• Hypoglycemia (most frequent, dose-dependent).
• Nausea, vomiting, abdominal discomfort.
• Weight gain.

Serious/Rare:

• Severe prolonged hypoglycemia.
• Hematologic effects: leukopenia, agranulocytosis, thrombocytopenia.
• Hepatotoxicity, cholestatic jaundice.
• Allergic skin reactions (rash, urticaria, photosensitivity).

• Increased hypoglycemia risk:
  – Insulin, other sulfonylureas, metformin, salicylates, sulfonamides, MAO inhibitors, beta-blockers, warfarin, alcohol.
• Reduced effect (hyperglycemia):
  – Corticosteroids, thiazide diuretics, phenytoin, rifampicin, thyroid hormones, oral contraceptives.
• Beta-blockers may mask hypoglycemia symptoms (tachycardia, tremor).

• Modern guidelines (ADA, EASD) recommend sulfonylureas as a second-line or third-line therapy for T2DM when metformin is insufficient or contraindicated.
• Due to hypoglycemia risk, newer agents (DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 analogs) are often preferred.
• Still widely used in low-resource settings due to cost-effectiveness.

• Store at 15–30°C, in a cool, dry place.
• Protect from light and moisture.
• Keep out of reach of children.