Repaglinide, a new oral glucose-lowering agent for the treatment of type 2 diabetes, has received approval for use as a single agent or in combination with metformin. Medical Letter consultants review the current data on this drug.

While repaglinide is structurally different from sulfonylureas, it also binds to adenosine triphosphate–sensitive potassium channels on pancreatic beta cells and increases the secretion of insulin. The drug is well absorbed when taken in the fasting state or with meals and reaches peak plasma levels within 30 to 60 minutes. It is rapidly metabolized in the liver and excreted mainly in the bile. Higher plasma concentrations may occur in patients with impaired hepatic function. As the serum repaglinide concentration increases, the plasma insulin level rises and usually returns to baseline before the next meal.

A clinical study of repaglinide therapy in patients already receiving a sulfonylurea demonstrated that the mean glycemic control was equivalent but that fasting glucose levels were lower with glyburide and postprandial peaks were lower with repaglinide. Repaglinide has been shown to be more effective when used with metformin than when either drug is used alone. Unpublished data indicate that 1 to 4 mg of repaglinide before meals lowers glycosylated hemoglobin by 1.3 to 1.9 percent.

Although no serious drug interactions have been reported with repaglinide, coadministration with ketoconazole, erythromycin and other drugs that are inhibitors of the cytochrome P₄₅₀ 3A4 enzyme system may increase serum concentrations of repaglinide.

The agent should also be used with caution in patients with impaired liver function. Although data are limited, repaglinide may not accumulate in patients with impaired renal function. Safety in pregnancy has not been determined.

Repaglinide is available as 0.5-, 1.0- and 2.0-mg tablets. The recommended starting dosage in patients who have not previously taken oral hypoglycemic drugs is 0.5 mg before each meal. If oral hypoglycemic agents have been used previously, the starting dosage may be 1 or 2 mg. The maximum dosage is 4 mg per meal for a maximum of four meals daily. If a meal is missed, that dose of repaglinide should be omitted.