Metformin and Nateglinide

Nateglinide is metabolized in the liver primarily by cytochrome P-450 2-C9 (70%) and 3-A4 (30%), and its metabolites are excreted renally. Therefore, no dose adjustment is necessary in patients with renal or hepatic insufficiency. Nateglinide is indicated for combination therapy with metformin in patients whose diabetes has not been adequately controlled with either agent alone. Patients whose diabetes has not been controlled by sulfonylureas or metformin should not be switched to nateglinide alone.

Although nateglinide is not appropriate in patients with advanced diabetes, especially where fasting blood glucose levels are greater than 200 mg/dL, it can be used very effectively in combination with metformin to enhance insulin sensitivity. A recent trial presented at the American Diabetes Association Scientific Sessions showed that nateglinide reduced postprandial glucose levels from 195 to 150 mg/dL in monotherapy and from 209 to 160 mg/dL in combination therapy with metformin and nateglinide. A1-C levels dropped an additional 0.8% when nateglinide was given to patients inadequately controlled on metformin monotherapy (20).

Other trials have shown more robust reduction of A1-C levels by 1.4% with the nateglinide/metformin combination, with fasting glucose reductions of 40 mg/dL. The nateglinide/metformin combination is ideal for overweight patients whose primary disturbance is postprandial hyperglycemia with A1-C less than 8%.

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