glimepiride
Sulfonylurea· Brands: Amaryl, SolosaPO
Mechanism of action
Glimepiride stimulates insulin release from pancreatic beta cells by binding to sulfonylurea receptors and closing ATP-sensitive potassium channels. This leads to membrane depolarisation, calcium influx, and increased insulin exocytosis. It may also improve peripheral insulin sensitivity.
Pharmacokinetics
Glimepiride is well absorbed after oral administration, with a bioavailability of about 100%. It is highly bound to plasma proteins (over 99%) and extensively metabolised by the liver, mainly via CYP2C9, to active metabolites. The elimination half-life is approximately 5 to 8 hours, and metabolites are excreted in both urine and faeces.
Indications & dosing
Type 2 diabetes mellitus (as monotherapy)
Starting dose 1 mg daily. Titrate at 1-2 week intervals. Usual maintenance 1-4 mg. Take with breakfast.
- adult · PO: 1–8 mg once daily · Starting dose 1 mg daily. Titrate at 1-2 week intervals. Usual maintenance 1-4 mg. Take with breakfast.
Type 2 diabetes mellitus (in combination with other antidiabetic agents)
Start at 1 mg daily. Adjust based on glycaemic response. Reduce insulin dose if used together.
- adult · PO: 1–8 mg once daily · Start at 1 mg daily. Adjust based on glycaemic response. Reduce insulin dose if used together.
Contraindications & precautions
- Type 1 diabetes mellitus · Sulfonylureas are ineffective without endogenous insulin secretion.
- Diabetic ketoacidosis · Requires insulin therapy.
- Hypersensitivity to glimepiride or other sulfonylureas · Includes allergic reactions to sulfonamides.
- Severe renal impairment · Risk of hypoglycaemia due to increased drug exposure.
- Severe hepatic impairment · Risk of hypoglycaemia due to impaired glucose regulation.
- Regularly monitor blood glucose and HbA1c to assess glycaemic control and detect hypoglycaemia.
- Initiate at low dose in elderly or renally impaired patients and titrate cautiously to reduce the risk of hypoglycaemia.
- Caution in patients with glucose-6-phosphate dehydrogenase deficiency, as sulfonylureas can cause haemolysis.
- Caution with concurrent beta-blockers or other drugs that mask the warning symptoms of hypoglycaemia.
- Advise patients to avoid excessive alcohol consumption, as it may precipitate hypoglycaemia.
Adverse effects
- Hypoglycaemiaserious
- Weight gain
- Gastrointestinal disturbances (e.g., nausea, diarrhoea)
- Skin reactions (e.g., rash, pruritus)
- Severe skin reactions (e.g., Stevens-Johnson syndrome)serious
- Haematological disorders (e.g., leucopenia, thrombocytopenia)serious
- Hepatic dysfunction (e.g., liver enzyme elevation, hepatitis)serious
Renal & hepatic adjustment
- eGFR 60–300: No dose adjustment required, but monitor blood glucose closely.
- eGFR 30–59: Use with caution; start at a low dose (e.g. 1 mg) and titrate carefully. Monitor for hypoglycaemia.
- eGFR 0–29: Avoid use; consider an alternative agent due to increased risk of prolonged hypoglycaemia. (avoid)
- Hepatic impairment (mild): No dose adjustment required, but monitor blood glucose regularly.
- Hepatic impairment (moderate): Use with caution; consider a lower starting dose and titrate slowly, with close glucose monitoring.
- Hepatic impairment (severe): Avoid use; glimepiride is contraindicated in severe hepatic impairment due to risk of hypoglycaemia. (avoid)
Monitoring, pregnancy & toxicity
- Blood glucose · Regularly, especially during dose titration and in renal/hepatic impairment.
- HbA1c · Every 3-6 months.
- Signs of hypoglycaemia · At each consultation.
- Renal function (serum creatinine, eGFR) · Periodically, particularly in elderly or those with renal impairment.
- Liver function tests · Periodically, especially in pre-existing liver disease.
- Pregnancy: Glimepiride is not recommended in pregnancy; insulin is the preferred treatment for glycaemic control. If a sulfonylurea is essential, seek specialist advice and convert to insulin before conception or as soon as pregnancy is confirmed.
- Toxicity: Hypoglycaemia · Administer oral glucose if conscious; if unconscious or unable to swallow, give IV glucose (e.g. 10-20% dextrose) or glucagon. Follow local hypoglycaemia protocols and monitor glucose levels.
- Toxicity: Severe or prolonged hypoglycaemia with neuroglycopenic symptoms · Admit to hospital, give IV dextrose infusion, and monitor blood glucose frequently for at least 24-48 hours to prevent recurrence.
Antidotes & reversal
- Dextrose IV with octreotide · IV dextrose plus octreotide for recurrent hypoglycaemia; observe 24-48 h for long-acting agent.
Clinical notes
Glimepiride is indicated for the treatment of type 2 diabetes mellitus, either alone or in combination with other antidiabetic agents such as metformin. It is taken once daily, usually before the first main meal. The starting dose is typically 1 mg daily, titrated according to blood glucose response. Hypoglycaemia is the most important adverse effect, especially in older patients, those with renal impairment, or after missed meals. Weight gain may occur. Regular monitoring of blood glucose and HbA1c is recommended. Severe hepatic impairment is a contraindication.
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BNF; local formulary