Generic Name

Repaglinide

Mechanism

• Targets the ATP‑sensitive K⁺ channel on pancreatic β‑cells, a class II sulfonylurea receptor.
• Rapidly binds these channels, causing depolarisation of the β‑cell membrane.
• Depolarisation opens voltage‑gated Ca²⁺ channels, increasing intracellular calcium.
• Elevated Ca²⁺ triggers exocytosis of insulin‑containing granules, raising plasma insulin levels.
• The effect begins within 15–30 min and lasts ~2–4 h, making it ideal for post‑meal glucose excursions.

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Pharmacokinetics

• Absorption: Oral bioavailability ≈ 32 %; absorption is fast (Cmax at 1–2 h).
• Distribution: ~ 86 % plasma protein binding; volume of distribution ~ 9 L.
• Metabolism: Primarily hepatic via CYP2C8 (≈ 70 %) and CYP3A4 (≈ 30 %).
• Elimination: Mainly biliary excretion of unchanged drug and metabolites; renal excretion < 10 %.
• Half‑life: 0.5–1 h; rapid clearance leads to the need for post‑prandial dosing.
• Food effect: High‑fat meals delay absorption slightly but do not alter overall exposure significantly.

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Indications

• Type 2 Diabetes Mellitus:
• Monotherapy for mild‑to‑moderate disease.
• Adjunctive therapy with metformin, sulfonylureas, or insulin when glucose targets are not met.
• Post‑prandial hyperglycaemia: specifically useful for controlling post‑meal glucose spikes.

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Contraindications

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Dosing

• Initial dose: 0.5 mg PO three times daily (after meals).
• Titration: Increase by 0.5 mg/day (max 1.5 mg) to achieve fasting glucose < 110 mg/dL, keeping dose ≤ 3 mg/day.
• Renal impairment:
• CrCl 30–49 mL/min → start 0.25 mg BID.
• CrCl < 30 mL/min → avoid; consider alternative agents.
• Hepatic impairment: No dosing data; use with caution and monitor liver enzymes.
• Administration: With meals to reduce hypoglycaemia risk; avoid taking on an empty stomach.

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Adverse Effects

*Notes*: Monitor for hypoglycaemic episodes, especially after dose mis‑timing or in elderly patients. Weight gain is less than with sulfonylureas but still observed.

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Monitoring

• Blood glucose: Self‑monitoring finger‑stick pre‑meal and 2 h post‑meal; adjust based on trend.
• HbA1c: Every 3 months or as per clinical guidelines.
• Renal function: Creatinine, eGFR at baseline and periodically.
• Liver enzymes: ALT, AST, bilirubin every 3 months if on long‑term therapy.
• Adverse events: Report hypoglycaemic episodes promptly.

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Clinical Pearls

• Post‑meal timing is key: Taking repaglinide with the first bite of a meal maximizes efficacy and minimizes hypoglycaemia.
• Short half‑life = rapid dosing: This allows for flexible meal‑time management but requires careful monitoring in patients with erratic eating schedules.
• CYP2C8/3A4 interactor: Strong inhibitors (e.g., ketoconazole) double exposure; strong inducers (e.g., rifampin) can reduce efficacy—dose adjustment or therapeutic drug monitoring is often necessary.
• Renal renormalization: Since renal clearance is minimal, kidney disease primarily impacts safety by increasing the risk of hypoglycaemia rather than reducing drug levels.
• Combination therapy: When paired with metformin, the risk of hypoglycaemia is comparable to sulfonylureas, but repaglinide offers the advantage of less weight gain and a lower hypoglycaemia risk profile during fasting states.

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• *Disclaimer*: This drug card is intended for educational purposes. Always refer to product labeling, local guidelines, and individual patient factors before prescribing.