glibenclamide
Sulfonylurea· Brands: Daonil, Euglucon, Semi-Daonil, GlynasePO
Mechanism of action
Glibenclamide is a sulfonylurea that stimulates insulin secretion from pancreatic beta cells by closing ATP-sensitive potassium channels, causing membrane depolarization and influx of calcium, which triggers insulin release. It also reduces hepatic glucose output and may enhance insulin sensitivity, but the primary effect is on insulin release.
Pharmacokinetics
Glibenclamide is completely absorbed after oral administration, reaching peak serum concentrations within 2 to 4 hours. It is highly bound to plasma proteins (about 99%), undergoes extensive hepatic metabolism to weakly active metabolites, and is eliminated in both urine and faeces. The elimination half-life is approximately 10 hours, with a duration of action lasting up to 24 hours.
Indications & dosing
Type 2 diabetes mellitus
Take with breakfast. Increase by 2.5-5 mg weekly based on blood glucose. Avoid in severe renal or hepatic impairment.
- adult · PO: 2.5–5 mg once daily · Take with breakfast. Increase by 2.5-5 mg weekly based on blood glucose. Avoid in severe renal or hepatic impairment.
Gestational diabetes mellitusoff-label
Off-label. Insulin is preferred. May increase to twice daily if needed, titrate cautiously.
- adult · PO: 2.5–5 mg once daily · Off-label. Insulin is preferred. May increase to twice daily if needed, titrate cautiously.
Contraindications & precautions
- Type 1 diabetes mellitus · Requires insulin therapy; sulfonylureas are ineffective.
- Diabetic ketoacidosis · Insulin is required for metabolic emergency.
- Severe renal impairment · Accumulation increases risk of hypoglycaemia; consider alternative.
- Severe hepatic impairment · Reduced metabolism and gluconeogenesis may precipitate hypoglycaemia.
- Pregnancy · Insulin is preferred; glibenclamide may be used in some cases under specialist advice.
- Use with caution in the elderly, as prolonged hypoglycaemia is more likely
- Monitor blood glucose regularly and adjust dose accordingly
- Caution in renal or hepatic impairment; consider alternative therapy
- Avoid alcohol due to risk of hypoglycaemia
- Check for interactions with drugs that potentiate hypoglycaemia, e.g. sulfonamides, salicylates, warfarin
- Advise the patient to recognise and manage symptoms of hypoglycaemia
Adverse effects
- Hypoglycaemiaserious
- Weight gain
- Gastrointestinal disturbances (e.g. nausea, diarrhoea)
- Skin reactions (e.g. rash, pruritus)
- Blood dyscrasias (e.g. leucopenia, thrombocytopenia)serious
- Hepatic dysfunctionserious
Interactions
- fluconazolemajorMonitor blood glucose closely, especially when starting or stopping fluconazole. Consider reducing the glibenclamide dose or switching to an alternative hypoglycaemic agent with a lower interaction potential.
Renal & hepatic adjustment
- eGFR 60+: No dose adjustment required.
- eGFR 30–60: Use with caution; consider dose reduction and close monitoring for hypoglycaemia.
- eGFR 0–30: Avoid use due to risk of prolonged hypoglycaemia. (avoid)
- Hepatic impairment (mild): No adjustment required.
- Hepatic impairment (moderate): Use caution; consider dose reduction and close monitoring.
- Hepatic impairment (severe): Avoid use; consider alternative agent. (avoid)
Monitoring, pregnancy & toxicity
- Blood glucose · regularly, especially after dose changes
- HbA1c · every 3-6 months
- Signs and symptoms of hypoglycaemia · at each review
- Renal function · at baseline and periodically, especially in the elderly
- Hepatic function · at baseline and periodically
- Pregnancy: Avoid in pregnancy. Insulin is the preferred treatment for diabetes in pregnancy. Glibenclamide may be used in selected cases under specialist advice, but is not recommended as first-line therapy.
- Toxicity: Hypoglycaemia (may be prolonged and severe) · Treat with oral glucose if conscious, or IV glucose if unconscious. Monitor blood glucose for at least 24 hours; may require hospital admission. Consider octreotide in refractory cases.
Antidotes & reversal
- Dextrose IV with octreotide · IV dextrose; octreotide 50-100 mcg SC/IV blocks further insulin release in recurrent sulfonylurea hypoglycaemia.
Clinical notes
Glibenclamide is indicated for type 2 diabetes mellitus when dietary measures alone are inadequate. It should be given with breakfast, or with the first main meal of the day, to reduce the risk of hypoglycaemia. The dose should be titrated according to blood glucose response and the lowest effective dose used. The risk of hypoglycaemia is increased in the elderly, in those with renal or hepatic impairment, and when meals are missed or delayed. It may cause weight gain, and the prescriber should be aware of possible interactions with other drugs, such as sulphonamides and alcohol. Note that glibenclamide is also known as glyburide in some countries. Avoid in patients with severe hepatic impairment, renal insufficiency, or adrenal and pituitary insufficiency; consider alternatives if the patient is pregnant or breastfeeding.
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BNF; local formulary