Metformin and Repaglinide

Combination therapy with metformin and repaglinide has shown additive effects, with reductions of A1-C of 1.4% compared with 0.4% with repaglinide alone and 0.3% with metformin alone. Because repaglinide is metabolized in the cytochrome P-450 3-

A4 enzyme system, drugs that are metabolized through this system (Rifampin, barbiturates, carbamazepine, certain statin drugs, amiodarone, benzodiazepines, sildenafil (Viagra), theophylline, and certain selective serotonin reuptake inhibitors) may increase repaglinide metabolism (19). Although in vitro data indicate that repaglinide metabolism may be inhibited by antifungal agents (such as ketoconazole and miconazole) or antibacterial agents (such as clarithromycin), systematically acquired data is not available on increased or decreased plasma levels with other cytochrome P-450 3-A4 inhibitors or inducers.

Risk of hypoglycemia is increased with the metformin/repaglinide combination compared with either agent alone. Repaglinide is not indicated for combination use with any sulfonylurea and should be avoided in the elderly, debilitated, or malnourished patients, or in patients with adrenal or pulmonary insufficiency. Repaglinide should not be used in patients with severe liver disease and should be used only with caution in patients with impaired hepatic function.

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