Glikazid MR

• Type 2 diabetes mellitus — adjunct to diet and exercise to improve glycaemic control in adults when lifestyle measures alone are insufficient.
• Monotherapy or combination therapy — may be used alone or in combination with metformin, DPP-4 inhibitors, SGLT2 inhibitors, or insulin (with appropriate adjustment and monitoring) for patients who require additional glucose lowering.
• Special situations (clinically used) — patients who require an oral secretagogue rather than insulin, provided there is preserved ß-cell function and no contraindication.

Important: individualize dose based on blood-glucose monitoring, HbA1c target, renal and hepatic function, age and risk of hypoglycaemia.

Immediate-release (standard) gliclazide

• Starting dose (drug-naïve adults): commonly 40 mg once daily (morning).
• Titration: increase slowly, typically by 40 mg increments at intervals of 1–2 weeks guided by fasting glucose; usual maintenance 80–160 mg/day; some patients may require up to 320 mg/day (divided doses if >160 mg/day).
• Administration: give with breakfast or the first main meal to reduce hypoglycaemia risk.

Modified-release (MR) gliclazide

• Starting dose: 30–60 mg once daily (product dependent).
• Usual maintenance: 60–120 mg once daily.
• Maximum MR dose: commonly 120 mg once daily.
• Administration: give once daily with breakfast; do not crush or chew MR tablets.

Pediatrics & pregnancy

• Pediatrics: not routinely recommended for children; use only in specialist settings.
• Pregnancy: not recommended as first-line — insulin is preferred for glycaemic control during pregnancy.

Elderly and special populations

• Elderly: start at lower doses and titrate cautiously; increased hypoglycaemia risk.
• Renal impairment: gliclazide is extensively metabolized; dose adjustment and careful monitoring required in moderate–severe renal impairment because of hypoglycaemia risk from reduced clearance of metabolites.
• Hepatic impairment: use with caution; severe hepatic dysfunction may increase risk of accumulation and hypoglycaemia — consider alternative therapy if hepatic function is markedly impaired.

Gliclazide is a sulfonylurea that stimulates insulin secretion from pancreatic β-cells. It binds selectively to the sulfonylurea receptor (SUR1) of ATP-sensitive potassium (KATP) channels in β-cell membranes, causing channel closure. Membrane depolarization opens voltage-dependent calcium channels, intracellular calcium rises and triggers exocytosis of insulin-containing granules. The increased circulating insulin lowers blood glucose. Gliclazide shows relatively selective activity at the pancreatic SUR1 subtype, which contributes to its glucose-dependent secretagogue effect.

• Absorption: Well absorbed after oral administration; food may modestly delay absorption—take with breakfast to reduce hypoglycaemia.
• Bioavailability: High oral bioavailability (formulation dependent).
• Distribution: Highly plasma protein bound (≈85–97%).
• Metabolism: Extensively metabolized in the liver to inactive metabolites, primarily via hepatic enzymes (CYP2C9 contributes).
• Elimination: Metabolites are excreted mainly in urine; only small amounts of unchanged drug are eliminated renally.
• Half-life: Intermediate elimination half-life (commonly reported in the range of approximately 8–20 hours depending on dose and individual factors).
• Onset & duration: Onset of glucose-lowering effect within hours; MR formulations provide prolonged effect allowing once-daily dosing.

• Pregnancy: Gliclazide is generally not recommended in pregnancy; insulin is the preferred agent because it allows better, controllable glycaemic management and avoids potential fetal exposure to oral hypoglycaemics. If pregnancy occurs on gliclazide, specialist review and likely switch to insulin is indicated.
• Lactation: Use during breastfeeding is generally not recommended because gliclazide can pass into breast milk and may cause hypoglycaemia in the infant; consider insulin or alternative therapy and discuss risks/benefits with a specialist.

• Primary class: Antidiabetic agent — sulfonylurea.
• Subclass: Second-generation sulfonylurea (commonly considered a “modern” sulfonylurea with different SUR selectivity).

• Known hypersensitivity to gliclazide, sulfonylureas or any excipients.
• Type 1 diabetes mellitus (insulin-dependent).
• Diabetic ketoacidosis (with or without coma).
• Severe hepatic impairment or conditions associated with significant liver dysfunction (unless specialist manages).
• Pregnancy and breastfeeding (unless a specialist decides otherwise).

• Hypoglycaemia: main and potentially serious risk. High risk with advanced age, renal impairment, irregular meals, alcohol, strenuous exercise, concomitant drugs that potentiate hypoglycaemia, or when combined with insulin or other secretagogues. Educate patients about recognition and self-treatment of hypoglycaemia.
• Elderly: increased sensitivity and higher hypoglycaemia risk — start low and titrate slowly.
• Hepatic and renal impairment: caution and close monitoring; adjust dose or choose alternative therapy when severe impairment present.
• Cardiovascular disease: use as part of an individualized plan; if switching from one sulfonylurea to another or to insulin, monitor carefully.
• Sulfonamide allergy: cross-reactivity with sulfonamide antibiotics is uncommon but possible — use caution in patients with severe sulfonamide hypersensitivity.
• Masking of hypoglycaemia symptoms: concomitant beta-blockers may blunt adrenergic warning signs of hypoglycaemia.

Very important / common

• Hypoglycaemia (mild to severe) — may be prolonged and require prompt carbohydrate administration; severe episodes may require glucagon or IV glucose.
• Weight gain — modest weight increase is common with sulfonylurea therapy.

Common / other

• Gastrointestinal disturbances (nausea, dyspepsia).
• Dizziness, headache.
• Cutaneous reactions (rash, pruritus).

Uncommon / rare but serious

• Haematological reactions (very rare; e.g., leucopenia, thrombocytopenia, aplastic anaemia reported with sulfonylureas).
• Hepatic dysfunction (elevated liver enzymes, cholestasis—rare).
• Severe allergic reactions (anaphylaxis, angioedema—rare).

Timing & dose-dependence

• Hypoglycaemia can occur at any time but is more likely soon after dose increases or if meals are missed; risk increases with higher doses and in susceptible populations.

• Drugs that increase risk of hypoglycaemia (potentiate sulfonylurea effect): other antidiabetic agents (insulin, meglitinides), some antibiotics (e.g., fluoroquinolones), some antifungals, some antimalarials, fibrates, non-selective beta blockers (may mask hypoglycaemic symptoms), ACE inhibitors (occasionally), and warfarin (interaction mechanisms may vary).
• Drugs that reduce gliclazide levels / efficacy: enzyme inducers (e.g., rifampicin, carbamazepine, phenytoin, St John’s wort) can increase metabolism and reduce effect.
• CYP interactions: gliclazide is largely metabolized hepatically (CYP2C9 involvement); strong CYP2C9 inhibitors may increase plasma levels and hypoglycaemia risk.
• Alcohol: may increase or unpredictably potentiate hypoglycaemia or cause disulfiram-like reactions with some sulfonylureas—advise moderation.
• Beta-blockers: may mask adrenergic symptoms of hypoglycaemia (tremor, tachycardia).
• Always review concomitant medicines and adjust dosing or monitoring as needed.

• Gliclazide remains an established oral option for glycaemic control in type 2 diabetes where secretagogue therapy is appropriate. Contemporary diabetes management guidelines emphasize individualized therapy: consider cardiovascular and renal comorbidities, hypoglycaemia risk, patient preferences and long-term goals when choosing gliclazide versus alternatives (e.g., metformin-based combinations, SGLT2 inhibitors, GLP-1 receptor agonists).
• Emphasis in modern practice: minimize severe hypoglycaemia, especially in older adults and those with comorbidities; use lowest effective dose and consider agents with lower hypoglycaemia risk in vulnerable patients.

• Store tablets at room temperature, typically 15–25°C (check product label).
• Protect from excessive heat, moisture and light.
• Keep in original packaging to protect from humidity; keep out of reach of children.
• Do not use past the expiry date printed on the pack.