The sulfonylureas are a class of agents that lower blood sugar as a result of increasing release of insulin from the pancreas. The sulfonylureas are used for the therapy of mild-to-moderate type 2 diabetes in conjunction with diet, and can be used alone or in combination with metformin, thiazolidinediones or other hypoglycemic agents. The sulfonylureas have been associated with rare cases of idiosyncratic drug induced liver disease with somewhat similar pattern of onset, injury and outcome.
While the sulfonylureas are derivatives of sulfonamides, they have no intrinsic antibacterial activity. They are believed to lower blood glucose levels by stimulating insulin release from pancreatic beta cells. However, their effects on blood glucose with chronic therapy are more complex, and the sulfonylureas may have extra-pancreatic actions that affect blood sugar, reducing hepatic clearance of insulin or increasing insulin sensitivity. The sulfonylureas have little effect in type 1 diabetes, in which there is a deficiency in insulin producing pancreatic beta cells. The sulfonylureas are widely used and are generally considered a first line of medication therapy for type 2 diabetes.
The sulfonylureas are divided into first and second generation agents, based upon their relative potency. All sulfonylureas share a similar structure, being substituted arylsulfonylureas. They differ on the basis of substitutions at the para positions at the two ends of the arylsulfonylurea molecule. The first generation sulfonylureas include chlorpropamide, tolazamide and tolbutamide. These agents are now rarely used although still available in the United States. The second generation sulfonylureas include gliclazide, glimepiride, glipizide and glyburide (known as glibenclamide outside of the United States) which are active in lower concentrations, are effective when taken once daily and have fewer of the troublesome dose related side effects of the first generation sulfonylureas, such as headache, nausea, anorexia, fatigue and paresthesias. The sulfonylureas (particularly the first generation agents) can also cause alcohol intolerance (flushing) through inhibition of alcohol dehydrogenase. The sulfonylureas are all labelled with a warning of increased risk of cardiovascular mortality with long term use.