gliclazide
Sulfonylurea· Brands: Diamicron, Diamicron MR, GlycronPO
Mechanism of action
Gliclazide stimulates insulin release from pancreatic beta cells by closing ATP-sensitive potassium channels, causing membrane depolarization and influx of calcium, which triggers exocytosis of insulin granules. This reduces blood glucose levels by increasing insulin secretion, particularly in response to meals.
Pharmacokinetics
Gliclazide is well absorbed from the gastrointestinal tract after oral administration and is extensively bound to plasma proteins. It is metabolized in the liver to inactive metabolites and excreted mainly in the urine. The elimination half-life is approximately 10 to 12 hours, allowing once-daily dosing with the modified-release formulation.
Indications & dosing
Type 2 diabetes mellitus (immediate-release formulation)
Start 40 mg daily, titrate to 80-160 mg daily. Doses above 160 mg should be divided into two doses.
- adult · PO: 40–160 mg once daily · Start 40 mg daily, titrate to 80-160 mg daily. Doses above 160 mg should be divided into two doses.
Type 2 diabetes mellitus (modified-release formulation)
Start 30 mg daily, titrate to 60-120 mg daily.
- adult · PO: 30–120 mg once daily · Start 30 mg daily, titrate to 60-120 mg daily.
Contraindications & precautions
- Type 1 diabetes mellitus · Ineffective; insulin is required
- Diabetic ketoacidosis · Insulin is required
- Severe hepatic impairment · Risk of hypoglycaemia due to impaired metabolism
- Severe renal impairment · eGFR < 30 mL/min; risk of accumulation and hypoglycaemia
- Hypersensitivity to gliclazide, other sulfonylureas, or excipients · Cross-hypersensitivity may occur
- Pregnancy · Insulin is preferred; gliclazide crosses the placenta
- Lactation · Excreted in breast milk; insulin is preferred
- Concomitant use with miconazole · Miconazole inhibits CYP2C9, increasing gliclazide levels and hypoglycaemia risk
- Take gliclazide with or immediately after the first main meal of the day to reduce the risk of hypoglycaemia.
- Monitor blood glucose regularly, particularly during treatment initiation, dose changes, or intercurrent illness.
- Use with caution in elderly or debilitated patients, who are more susceptible to hypoglycaemia; consider a lower initial dose.
- Caution in moderate renal or hepatic impairment; dose adjustment may be needed and severe impairment is contraindicated.
- Educate patients to recognise and manage hypoglycaemia, e.g. carrying fast-acting carbohydrate and glucagon kits where appropriate.
- Advise patients that alcohol may enhance the hypoglycaemic effect; moderation is recommended.
Adverse effects
- Hypoglycaemiaserious
- Weight gain
- Gastrointestinal disturbances (nausea, diarrhoea, abdominal pain)
- Skin rash
- Blood dyscrasias (leucopenia, thrombocytopenia)serious
- Hepatic dysfunction (e.g. cholestatic jaundice)serious
- Severe skin reactions (e.g. Stevens-Johnson syndrome)serious
Interactions
- fluconazolemajorMonitor blood glucose closely before and during therapy. Consider reducing the gliclazide dose or selecting an antifungal that does not inhibit CYP2C9, such as terbinafine. Advise the patient about the signs and symptoms of hypoglycaemia and to carry a fast-acting carbohydrate. If gliclazide dose is adjusted, reassess after stopping fluconazole.
- ramiprilmoderateMonitor blood glucose more frequently when ramipril is started or its dose is changed. Advise the patient on recognising and managing hypoglycaemia. If hypoglycaemia occurs, consider reducing the gliclazide dose. This combination is not contraindicated, but close monitoring is recommended.
Renal & hepatic adjustment
- eGFR 30–60: Use with caution. Initiate at a lower dose and titrate carefully to avoid hypoglycaemia.
- eGFR 0–29: Avoid use due to increased risk of hypoglycaemia and accumulation of active metabolites. (avoid)
- Hepatic impairment (mild): Use with caution. Monitor blood glucose closely and consider dose reduction.
- Hepatic impairment (moderate): Use with caution. Consider dose reduction and monitor for hypoglycaemia.
- Hepatic impairment (severe): Avoid use due to increased risk of hypoglycaemia and impaired hepatic metabolism. (avoid)
Monitoring, pregnancy & toxicity
- Blood glucose (fasting and postprandial) · Regularly, as clinically indicated
- HbA1c · Every 3 months
- Renal function (serum creatinine, eGFR) · At baseline and periodically, especially in renal impairment
- Liver function tests · At baseline and periodically, especially in hepatic impairment
- Signs and symptoms of hypoglycaemia · At each review
- Pregnancy: Not recommended in pregnancy. Insulin is the preferred treatment. If used, specialist supervision and close foetal/neonatal monitoring are required.
- Toxicity: Hypoglycaemia (sweating, tremor, confusion, seizures, coma) · Give oral glucose if conscious; if unconscious, give IV glucose or IM glucagon. Monitor blood glucose for 24-48 h due to prolonged duration of action.
- Toxicity: Prolonged/recurrent hypoglycaemia · Admit to hospital; treat with repeated glucose or IV infusion. Consider activated charcoal for recent overdose.
Antidotes & reversal
- Dextrose IV with octreotide · IV dextrose; octreotide for recurrent episodes; elderly and renal impairment increase risk and duration.
Clinical notes
Gliclazide is used as a second-line treatment for type 2 diabetes mellitus when diet and exercise are insufficient, particularly in patients who are not overweight. It can cause hypoglycaemia, especially in elderly patients or those with renal impairment. Monitor blood glucose levels and HbA1c regularly. Caution in hepatic impairment and with concurrent use of beta-blockers or alcohol.
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BNF; local formulary