Sulfonylureas

Sulfonylureas are a class of oral medications used in the treatment of type 2 diabetes. They act by increasing endogenous insulin secretion from pancreatic beta cells. They are typically considered after diet, exercise, and metformin have not achieved adequate glycemic control.

Mechanism of action: They bind the SUR1 subunit of ATP-sensitive potassium channels on pancreatic beta cells, causing channel closure, membrane depolarization, calcium influx, and insulin release. This effect depends on functional beta cells, but insulin can be released even when glucose is not high, increasing the risk of hypoglycemia. Some agents may also have modest effects on peripheral insulin sensitivity or hepatic glucose production.

Pharmacokinetics and generations: First-generation agents (tolbutamide, chlorpropamide, acetohexamide, tolazamide) are less potent and have longer half-lives with more drug interactions. Second-generation agents (glipizide, glyburide/glibenclamide, glimepiride) are more potent and generally have more favorable pharmacokinetic profiles, with shorter onsets in many formulations.

Clinical use and safety: Sulfonylureas are prescribed for adults with type 2 diabetes when lifestyle modification and metformin are insufficient. They are not used for type 1 diabetes or diabetic ketoacidosis and are generally avoided in pregnancy; insulin is preferred during pregnancy. Dosing should be cautious in older adults and in those with renal or hepatic impairment due to an increased risk of hypoglycemia.

Adverse effects and interactions: The main adverse effect is hypoglycemia, often accompanied by weight gain. Less common effects include hypersensitivity reactions. Alcohol, beta-blockers, and several drug interactions can alter their effect or mask hypoglycemia; dose adjustments may be needed in renal impairment.

Examples: First generation include tolbutamide, chlorpropamide, acetohexamide, and tolazamide; second generation include glipizide, glyburide (glibenclamide), and glimepiride.