Glipizide is a second-generation sulfonylurea in which the substitutions on the arylsulfonylurea nucleus are large, relatively nonpolar groups. This chemical change increases the intrinsic hypoglycemic activity of the molecule 100-fold on a weight basis compared to first-generation agents. In addition, the pharmacokinetic properties, spectrum and severity of side effects and metabolism of this agent are somewhat different from those of first-generation sulfonylureas. The most important component of the antidiabetic action of glipizide is its effect in potentiating insulin action. Glipizide-mediated increases in nutrient-stimulated insulin secretion may contribute to its antidiabetic action. The drug is effective in controlling the blood glucose in patients with noninsulin-dependent diabetes mellitus. It is at least as effective as and probably more effective than first-generation sulfonylureas in controlling hyperglycemia in diabetes. Glipizide is relatively free of serious side effects and is contraindicated principally in patients with significant liver or kidney disease.