Mechanism of action of the second-generation sulfonylurea glipizide

Glipizide, a second-generation sulfonylurea, has potent antidiabetic actions in patients with noninsulin-dependent diabetes mellitus. The effects of glipizide treatment on insulin sensitivity, glucose-mediated insulin secretion, and glucose utilization were measured in newly diagnosed or untreated patients with noninsulin-dependent diabetes mellitus. The data indicate that the antidiabetic action of glipizide is primarily mediated by a potentiation of insulin action and, to a less significant and more variable degree, by an increase in nutrient-mediated insulin secretion. Studies in normal mice and dogs show that glipizide potentiation of insulin action is associated with an increase in plasma membrane insulin receptor number, involves some postreceptor events, and is significantly greater on peripheral uptake of glucose than suppression of hepatic glucose production. The initial event in glipizide action on beta cells appears to be binding to a specific plasma membrane receptor.