Generic Name

Glimepiride

Mechanism

• Sulfonylurea class: Non‑metabolizable analog of first‑generation agents.
• Binds to SUR₁ on β‑cell K⁺ channels → channel closure → increased intracellular Ca²⁺ → insulin secretion.
• Effect is dose‑dependent and persists until drug is eliminated.

Pharmacokinetics

• Absorption: Oral bioavailability ~60–80 %; well absorbed within 3 h.
• Distribution: Highly protein‑bound (~95 % to albumin).
• Metabolism: Extensive hepatic oxidation via CYP2C9 and CYP3A4 to inactive metabolites.
• Elimination: Primarily renal (≈70 % urinary excretion); half‑life ≈12 h, therapeutic window ~24 h.
• Drug interactions: Inhibitors/inducers of CYP2C9 (e.g., warfarin, phenytoin, rifampin) alter levels.

Indications

• Type 2 diabetes mellitus:
• Monotherapy in mild‑to‑moderate disease.
• Adjunct to diet, exercise, or other antihyperglycemics (metformin, thiazolidinediones) when HbA1c target not achieved.

Contraindications

• Contraindications: Hypersensitivity to sulfonylureas, type 1 diabetes, severe diabetic ketoacidosis.
• Warnings:
• Hypoglycaemia risk ↑ with renal/hepatic impairment, elderly, or concomitant agents (e.g., insulin, meglitinides).
• Weight gain ~0.5–1 kg/year.
• Cardiovascular: Not proven protective; monitor for heart failure or arrhythmias.

Dosing

• Starting dose: 1 mg PO once daily (usually with breakfast).
• Titration: Increase by 0.5–1 mg increments every 1–2 weeks, max 4 mg/day.
• Administration: Take consistently at same time each day; avoid skipping doses.
• Renal/hepatic dysfunction: Reduce dose or lengthen interval; avoid if CrCl <30 mL/min.

Adverse Effects

• Common:
• Hypoglycaemia (most frequent).
• Weight gain.
• Nausea, flatulence.
• Serious:
• Severe hypoglycaemia (especially after missed meals or exercise).
• Hypersensitivity reactions (rash, urticaria).
• Hypotension in patients with heart failure (rare).

Monitoring

• Fasting plasma glucose: Twice weekly until stable, then monthly.
• HbA1c: Every 3 months to assess control.
• Renal/hepatic function: Every 6–12 months or sooner if clinically indicated.
• Weight: At each visit.
• Hypoglycaemia episodes: Document and adjust dose.

Clinical Pearls

• “Dose‑to‑Blood” Principle – Start low and titrate gradually; patients often require 1–2 mg total daily dose.
• Avoid Late‑Night Dosing – Improves hypoglycaemia profile; preferred for patients with irregular meals.
• Renal Function ≠ Dose – Even mild renal impairment warrants dose reduction to mitigate hypoglycaemia.
• Pregnancy – Classified FDA pregnancy category C; use only if benefits outweigh risks; monitor maternal glycaemia closely.
• Drug‑Drug Check – Concomitant warfarin can increase bleeding risk; monitor INR.

Glimepiride remains a cornerstone of type 2 diabetes therapy due to its predictable pharmacodynamics, oral route, and ability to provide durable glycaemic control when appropriately monitored.