sulfonylurea

Sulfonylureas are a class of oral medications used to lower blood glucose in type 2 diabetes. They act as insulin secretagogues, prompting the pancreas to release more insulin in response to elevated blood glucose.

Mechanism of action: Sulfonylureas bind to the sulfonylurea receptor 1 (SUR1) on pancreatic beta cells, which closes the ATP-sensitive potassium (KATP) channel. This depolarizes the cell membrane, opens voltage-gated calcium channels, increases intracellular calcium, and triggers the exocytosis of insulin-containing granules. Effective action requires some residual beta-cell function.

Generations and examples: There are first-generation agents such as chlorpropamide, tolbutamide, acetohexamide, and carbutamide, and second-generation agents including glipizide, glyburide (glibenclamide), and glimepiride. Second-generation sulfonylureas are more potent and are typically used at lower doses, with fewer clinically significant drug interactions, making them more commonly prescribed.

Clinical use and considerations: Sulfonylureas are used as monotherapy or in combination with other antidiabetic agents (for example metformin) in type 2 diabetes when diet and exercise alone do not achieve glycemic targets. They are not effective in type 1 diabetes or in cases of advanced beta-cell failure. In gestational diabetes, glyburide has been used in some settings but insulin remains the standard in many guidelines; practice varies by country and guideline.

Adverse effects and safety: The most notable adverse effect is hypoglycemia, with risk factors including older age, renal or hepatic impairment, and concomitant use of other glucose-lowering drugs. Weight gain is common. Rare hypersensitivity reactions can occur; chlorpropamide and some agents can cause disulfiram-like reactions with alcohol. Drug interactions often involve hepatic metabolism, particularly CYP2C9.