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Gliclazide
Gliclazide, a second-generation sulfonylurea, is a cornerstone oral antidiabetic agent used to manage type 2 diabetes mellitus (T2DM). Renowned for its efficacy in stimulating insulin secretion, it is often prescribed when lifestyle modifications and metformin are insufficient. This article integrates evidence from the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to detail its mechanism of action, clinical uses, dosing, side effects, precautions, drug interactions, and pharmaceutical nomenclature.
Gliclazide exerts its glucose-lowering effects through:
- Pancreatic Beta-Cell Stimulation:
- Binds to ATP-sensitive potassium (Kₐₜₚ) channels on pancreatic β-cells, causing channel closure. This depolarizes the cell membrane, opening voltage-gated calcium channels and triggering insulin secretion (Lippincott).
- Extrapancreatic Effects:
- May improve peripheral insulin sensitivity and reduce hepatic glucose production over time, though this is secondary to its primary insulinotropic action (Lange).
- BNF-Approved Indications:
- Type 2 Diabetes Mellitus: Monotherapy or combined with other agents (e.g., metformin, SGLT2 inhibitors) when diet/exercise and first-line therapies fail.
- Off-Label Uses:
- Limited evidence for use in gestational diabetes or monogenic diabetes (e.g., MODY), though not routinely recommended (Lange).
- Standard Release Tablets:
- Initial Dose: 40–80 mg daily, taken with breakfast.
- Maintenance: Gradually increase to 160–320 mg daily in divided doses (max 320 mg/day) (BNF).
- Modified-Release (MR) Formulation:
- Initial Dose: 30 mg once daily, adjusted monthly based on response (max 120 mg/day) (BNF).
- Renal/Hepatic Impairment:
- Avoid in severe renal impairment (eGFR <30 mL/min/1.73m²) or hepatic failure due to hypoglycemia risk (BNF).
- Hypoglycemia: Most frequent adverse effect, especially in elderly or malnourished patients.
- Gastrointestinal: Nausea, dyspepsia, diarrhea.
- Weight Gain: Moderate (2–4 kg) due to insulin-mediated anabolism (Lippincott).
- Rare but Serious:
- Hypersensitivity: Skin rashes, erythema multiforme.
- Hematologic: Leukopenia, thrombocytopenia (BNF).
- Contraindications:
- Type 1 diabetes, ketoacidosis, severe renal/hepatic impairment (BNF).
- Regular blood glucose checks, HbA1c (target ≤7% for most adults).
- Renal function (eGFR) and liver enzymes annually (Lange).
- Elderly: Higher hypoglycemia risk; start with low doses (e.g., 40 mg/day).
- Pregnancy: Avoid (BNF category not recommended; switch to insulin).
- Hypoglycemia Risk Enhancers:
- Beta-Blockers: Mask hypoglycemia symptoms (e.g., tachycardia).
- Alcohol: Potentiates hypoglycemia and disulfiram-like reactions (BNF).
- CYP2C9 Inhibitors:
- Fluconazole, Warfarin: Increase gliclazide levels, raising hypoglycemia risk (Lippincott).
- Hyperglycemia Inducers:
- Corticosteroids, Thiazides: Antagonize glucose-lowering effects (Lange).
- Generic Name: Gliclazide.
- Brand Names:
- UK (BNF): Diamicron®, Zicron®, Nazdol®.
- Modified-Release: Diamicron MR®, Gliclazide XL®.
