Sulfonylurea

glyburide, glimepiride, glipizide

MOA

They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present.

binds to the regulatory subunits of the ATP-dependent K+ channel on pancreatic beta cells --> membrane depolarization --> influx of calcium --> release of insulin by exocytosis

(N.B. also decrease hepatic glucose production and increase insulin receptor sensitivity)

SE:

Hypoglycemia, esp. in elderly, risk also increased by exercise, missed meals, chronic malnourishment, or organ dysfunction (renal, cardiac, GI, etc.) or after a hospital admission

(may have persistent/recurrent hypoglycemic attacks, particularly with longer-acting ones such as glyburide and glimepride; note that glipizide is short-acting and has a significantly lower incidence of hypoglycemia)

Weight gain

Rarer adverse effects

• hyponatraemia secondary to syndrome of inappropriate ADH secretion (SIADH)
• bone marrow suppression
• hepatotoxicity (typically cholestatic)
• peripheral neuropathy

Sulfonylureas should be avoided in breastfeeding and pregnancy.