CriticalLipid-lowering agent of the fibrate class×Meglitinide – short-acting oral insulin secretagogue
Updated · Methodology
Mechanism
Repaglinide is metabolised by CYP2C8 and taken up by the liver through OATP1B1. Gemfibrozil blocks both routes at once and repaglinide clearance falls. In healthy volunteers, gemfibrozil 600 mg twice daily for 3 days raised repaglinide AUC 8.1-fold and the plasma concentration 7 hours post-dose 28.6-fold.
Symptoms
Severe hypoglycemia: cold sweat, tremor, confusion, seizures, loss of consciousness. The episode arrives later than usual and lasts longer, because repaglinide is cleared many times more slowly. Nocturnal hypoglycemia carries the greatest danger: the person does not wake at the first signs.
Management
The FDA label prohibits this combination, and no dose-reduction workaround exists. If both drugs are already prescribed, repaglinide is switched to an agent with a different metabolic route rather than dose-reduced. During the switch, blood glucose is self-monitored frequently for the first days: CYP2C8 inhibition by the gemfibrozil glucuronide is irreversible and resolves as the enzyme is replaced, not within hours.
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Sources
- FDA: LOPID (gemfibrozil tablets, USP) prescribing information (2024)– FDA DailyMed, LOPID (gemfibrozil), Parke-Davis Div of Pfizer, 2024
- AEMPS: Ficha técnica: Gemfibrozilo (nº registro 61831), sección 4.3 (2025)– AEMPS, CIMA, nº registro 61831, sección 4.3
- AEMPS: Ficha técnica: Repaglinida (nº registro 72669), sección 4.3 (2022)– AEMPS, CIMA, nº registro 72669, revisión 05/2022, sección 4.3