Gliclazide exerts its glucose-lowering effects through:

1. 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).
2. Extrapancreatic Effects:
   • May improve peripheral insulin sensitivity and reduce hepatic glucose production over time, though this is secondary to its primary insulinotropic action (Lange).

1. 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.
2. 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).

1. • 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).
2. 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).

1. Hypoglycemia Risk Enhancers:
   • Beta-Blockers: Mask hypoglycemia symptoms (e.g., tachycardia).
   • Alcohol: Potentiates hypoglycemia and disulfiram-like reactions (BNF).
2. CYP2C9 Inhibitors:
   • Fluconazole, Warfarin: Increase gliclazide levels, raising hypoglycemia risk (Lippincott).
3. 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®.