14.01.6 Sulfonylureas

The sulfonylureas are a group of oral hypoglycemic agents, which includes glibenclamide. The sulfonylureas inhibit the K⁺_ATP channel in the pancreatic beta cells to increase insulin secretion (Figure 14.1). The sulfonylureas are active after oral administration and are given orally once or twice daily, which is a major advantage over insulin. Their disadvantage over insulin is that they are not effective in type 1 diabetes, as they require the presence of insulin to work. The major adverse effect of the sulfonylureas is hypoglycemia, and the hypoglycemia is enhanced by alcohol. Thus, as with insulin, there is a need to check plasma glucose regularly to make sure there is no hypoglycemia and that the glucose levels are under control. Unfortunately, the sulfonylureas cause a weight gain of a few kilograms, which tends to counter some of the benefit with these agents. The oral sulfonylureas may become less effective with time, this is due to the progression of beta-cell failure or of the insulin resistance, making less endogenous insulin available or making the available insulin less effective. When this happens, the type 2 diabetic, may have to proceed to insulin replacement therapy.