Introduction

For many years sulfonylureas have been the mainstay of oral antidiabetic therapy based on their insulinotropic action on beta cells in the pancreatic islets of Langerhans. Several alternative oral agents have now become available, broadening the spectrum of therapeutic alternatives. However, insulinotropic agents target one of the deficits that characterize diabetes mellitus type 2, namely a relative insufficiency of insulin secretion. Their therapeutic efficacy has been proven in several smaller trials, and in a large randomized prospective trial in type 2 diabetes—the U.K. Prospective Diabetes Study (UKPDS)—and was shown to be similar to the administration of insulin (1). A recent study in the United States compared the glucose-lowering potential of insulin with sulfonylureas in a setting of treatment by family practitioners, and found similar potency for either treatment (2). Insulin lowered the glycosylated hemoglobin (HbA1c) by 0.8% and the sulfonylurea by 1.1%, which is comparable to the outcome observed in the UKPDS.

A number of different insulinotropic agents have been developed, which differ in their insulinotropic potency, duration of action, routes of elimination, and noninsulinotropic additional and side effects (3). Very recently, an additional group of insulinotropic agents acting on the sulfonylurea receptor has become available. These compounds are termed meglitinides, and presently consist of the benzoic acid derivative repaglinide and the tryptophane derivative nateglinide.

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