Sulfonylureas are the most widely prescribed drugs in the treatment of type II diabetes mellitus. The initial sulfonylureas were introduced nearly 50 years ago and were derivatives of the antibacterial sulfonamides.
The primary mechanism of action of the sulfonylureas is direct stimulation of insulin release from the pancreatic beta cells. In the presence of viable pancreatic Beta-cells, sulfonylureas enhance the release of endogenous insulin, thereby reducing blood glucose levels. At higher doses, these drugs also decrease hepatic glucose production, and the second-generation sulfonylureas may possess additional extrapancreatic effects that increase insulin sensitivity, though the clinical significance of these pharmacological effects is unclear.
Classification of sulfonylureas
Mechanism of action on insulin secretion
In the basal state, the plasma membrane of the β cell is hyperpolarized, and the rate of insulin secretion from the cell is low. When glucose is available, it enters the cell via GLUT2 transporters in the plasma membrane and is metabolized to generate intracellular ATP. ATP binds to and inhibits the plasma membrane K+/ATP channel. Inhibition of the K+/ATP channel decreases plasma membrane K+ conductance; the resulting depolarization of the membrane activates voltage-gated Ca2+ channels and thereby stimulates an influx of Ca2+. Ca2+ mediates fusion of insulin-containing secretory vesicles with the plasma membrane, leading to insulin secretion.
The K+/ATP channel, an octamer composed of Kir6.2 and SUR1 subunits, is the target of several physiologic and pharmacologic regulators. ATP binds to and inhibits Kir6.2, while sulfonylureas bind to and inhibit SUR1; these agents promote insulin secretion.
Therapeutic uses, side effects and contraindications 
Sulfonylureas are used to control hyperglycemia in type 2 Diabetes mellitus affected patients who cannot achieve appropriate control with changes in diet alone. In all patients, continued dietary restrictions are essential to maximize the efficacy of the sulfonylureas.
The major adverse effect is hypoglycemia resulting from oversecretion of insulin; therefore, should be used cautiously in patients who are unable to recognize or respond to hypoglycemia
Contraindications to the use of these drugs include type 1 DM, pregnancy, lactation, and for the older preparations, significant hepatic or renal insufficiency.