“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Sunday, July 27, 2025

Gliclazide


Gliclazide is an oral hypoglycemic (antidiabetic) agent classified under the sulfonylurea drug class. It is commonly used in the management of type 2 diabetes mellitus (T2DM) to improve glycemic control when diet, physical activity, and weight reduction alone are insufficient. Gliclazide lowers blood glucose by stimulating insulin secretion from functioning pancreatic β-cells. It is not used in type 1 diabetes or in diabetic ketoacidosis.

Gliclazide is marketed in both immediate-release (IR) and modified-release (MR/XL) forms. The modified-release formulations allow once-daily dosing and are generally preferred due to better tolerability and adherence.

Pharmacological Classification

  • Therapeutic class: Oral antidiabetic (sulfonylurea)

  • ATC Code: A10BB09

  • Drug class: Second-generation sulfonylurea

  • Legal status: Prescription-only medicine (POM)

Mechanism of Action

Gliclazide acts primarily by stimulating pancreatic β-cells to secrete insulin. It achieves this through:

  1. Binding to sulfonylurea receptor 1 (SUR1) on the pancreatic β-cell membrane

  2. Inhibition of ATP-sensitive potassium (KATP) channels, leading to:

    • Membrane depolarization

    • Opening of voltage-dependent calcium channels

    • Influx of calcium

    • Exocytosis of insulin-containing granules

This glucose-independent mechanism increases insulin release regardless of blood glucose levels, which increases the risk of hypoglycemia compared to some other oral agents like metformin.

Gliclazide also has antioxidant and hemorheological properties, and in some studies, has shown microvascular benefits, particularly in reducing diabetic complications.

Indications

Approved Indications

  • Type 2 diabetes mellitus (T2DM), particularly in:

    • Non-obese or mildly obese adults

    • Individuals who cannot achieve glycemic control with diet and exercise alone

Off-label or Additional Considerations

  • May be considered as second-line therapy after metformin

  • May be combined with other oral antidiabetic agents (e.g., metformin, DPP-4 inhibitors, SGLT2 inhibitors)

Dosage and Administration

Immediate-Release (IR) Formulation

  • Starting dose: 40–80 mg once or twice daily

  • Titrated up to 160 mg twice daily (maximum: 320 mg/day)

  • Best taken 30 minutes before meals to reduce risk of hypoglycemia

Modified-Release (MR/XL) Formulation

  • Starting dose: 30 mg once daily with breakfast

  • Maintenance dose: 30–120 mg once daily

  • Maximum: 120 mg/day

  • Tablets must be swallowed whole; do not crush or chew

Elderly or Hepatic Impairment

  • Start at lower end of dosage range and monitor closely

Pharmacokinetics

  • Absorption: Well absorbed orally; modified-release forms provide smoother pharmacokinetics

  • Bioavailability: >95%

  • Time to peak concentration:

    • IR: ~2–4 hours

    • MR: ~6–12 hours

  • Half-life: 10–12 hours (MR); 4–6 hours (IR)

  • Metabolism: Liver (CYP2C9); inactive metabolites

  • Excretion: Mainly in urine (~60–70%), also in feces (~10%)

Contraindications

  • Type 1 diabetes mellitus

  • Diabetic ketoacidosis

  • Severe renal impairment

  • Severe hepatic impairment

  • Known hypersensitivity to gliclazide or other sulfonylureas/sulfonamides

  • Pregnancy and breastfeeding

  • Patients receiving treatment with miconazole (systemic or oral gel) due to risk of severe hypoglycemia

Precautions and Warnings

  • Hypoglycemia risk:

    • Higher in elderly, patients with irregular meals, or renal/hepatic dysfunction

  • Renal impairment:

    • Use with caution; MR formulation preferred due to lower risk of hypoglycemia

  • Liver dysfunction:

    • Increased half-life and reduced clearance; monitor liver function

  • Adrenal/pituitary insufficiency:

    • May increase sensitivity to sulfonylureas

  • Weight gain:

    • Associated with insulin-stimulating agents

  • Alcohol:

    • May potentiate hypoglycemic effects or cause disulfiram-like reaction

Adverse Effects

Common (1–10%)

  • Hypoglycemia (especially with IR formulation or missed meals)

  • Nausea

  • Dyspepsia

  • Headache

  • Weight gain

Uncommon (0.1–1%)

  • Rash, pruritus

  • Abnormal liver function tests

  • Hepatitis (rare, reversible)

Rare (<0.1%)

  • Aplastic anemia, agranulocytosis, thrombocytopenia

  • Cholestatic jaundice

  • Hyponatremia (SIADH-like picture)

  • Photosensitivity

Serious

  • Severe hypoglycemia: confusion, loss of consciousness, seizures

  • Hematologic disorders (rare but serious)

Drug Interactions

Drugs that Increase Hypoglycemia Risk

  • Other antidiabetic agents (insulin, metformin, GLP-1 agonists)

  • NSAIDs (e.g., ibuprofen, aspirin in high doses)

  • Alcohol

  • Miconazole (contraindicated, especially oral gel)

  • Fluconazole, ketoconazole

  • Beta-blockers: may mask hypoglycemia symptoms (e.g., tremor, tachycardia)

  • ACE inhibitors

  • MAO inhibitors

Drugs that May Reduce Gliclazide Efficacy

  • Corticosteroids

  • Thiazide diuretics

  • Rifampicin

  • Danazol

  • Sympathomimetics (e.g., salbutamol)

  • Estrogens and progestogens (high dose contraceptives)

Monitoring Parameters

  • Fasting blood glucose (FBG) and HbA1c

  • Renal function (eGFR, creatinine)

  • Liver function tests

  • Signs of hypoglycemia (especially in elderly or underweight patients)

  • Body weight

  • Periodic complete blood count (for hematologic side effects)

Use in Pregnancy and Lactation

  • Pregnancy: Contraindicated; insulin is preferred for glycemic control during pregnancy

  • Breastfeeding: Not recommended; risk of hypoglycemia in the nursing infant

Use in Special Populations

Elderly

  • More susceptible to hypoglycemia; start at lower doses and monitor closely

Renal Impairment

  • Use with caution; dose adjustment may be necessary

Hepatic Impairment

  • Risk of accumulation; monitor liver enzymes and hypoglycemia risk

Comparative Benefits

  • Compared to other sulfonylureas:

    • Gliclazide is associated with a lower risk of hypoglycemia than glibenclamide (glyburide)

    • May have protective microvascular benefits, such as reduced retinopathy progression

  • Compared to metformin:

    • Higher risk of hypoglycemia and weight gain

    • Not first-line unless metformin is contraindicated or not tolerated

Patient Counseling

  • Take the medication at the same time daily, preferably with breakfast

  • Never skip meals; increases risk of hypoglycemia

  • Learn to recognize symptoms of low blood sugar: sweating, shakiness, dizziness, confusion

  • Carry fast-acting sugar (glucose tablets, sweets) in case of hypoglycemia

  • Avoid alcohol, which can increase the risk of low blood sugar

  • Continue to monitor blood glucose regularly as advised

  • Do not drive or operate machinery if you experience hypoglycemic episodes

Brand Names

  • Diamicron® / Diamicron MR® (Servier)

  • Zicron®

  • Gliclazide Accord®

  • Nidiabet®

  • Gliclazide Teva®

  • Available as generic under various manufacturers globally




on
Labels:

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)