What is the half-life of sulfonureas (sulfonylureas)?

Half-Life of Sulfonylureas

Sulfonylureas have varying half-lives, with first-generation agents like chlorpropamide having much longer half-lives (approximately 34 hours) compared to second-generation agents like glipizide (3.8-4.3 hours) and glibenclamide/glyburide (1.8-5 hours). 1

Different Types of Sulfonylureas and Their Half-Lives

First-Generation Sulfonylureas

• Chlorpropamide has a very long half-life of approximately 34 hours 1
• Tolbutamide has a half-life of approximately 7 hours 1
• First-generation sulfonylureas should generally be avoided in patients with chronic kidney disease (CKD) due to their prolonged half-lives and increased risk of hypoglycemia 2

Second-Generation Sulfonylureas

• Glipizide has a half-life of 3.8-4.3 hours 3, 1
• Glibenclamide (glyburide) has a half-life of 1.8-5 hours in healthy individuals, but may be prolonged in certain patients 1
• Glimepiride has a shorter half-life than first-generation agents but longer than glipizide 4
• Gliclazide has a moderate half-life among second-generation agents 4

Clinical Implications of Sulfonylurea Half-Lives

Risk of Hypoglycemia

• Longer-acting sulfonylureas with extended half-lives (particularly chlorpropamide) are associated with a higher risk of prolonged and potentially severe hypoglycemia 2, 5
• First-generation sulfonylureas have a substantially greater risk of hypoglycemia than second-generation agents like glipizide, glimepiride, and gliclazide 2
• The risk of hypoglycemia is particularly concerning in elderly patients and those with renal impairment 2

Special Considerations in Renal Impairment

• Progressive decreases in kidney function result in decreased clearance of sulfonylureas and their active metabolites, which can prolong their half-lives 2
• In patients with CKD, glipizide is the preferred sulfonylurea as it does not have active metabolites and does not significantly increase the risk of hypoglycemia 2
• First-generation sulfonylureas should be completely avoided in patients with CKD 2

Comparison with Other Insulin Secretagogues

• Glinides (repaglinide, nateglinide) have shorter circulating half-lives than sulfonylureas and must be administered more frequently 2
• The shorter half-life of glinides may contribute to a lower risk of hypoglycemia compared to some sulfonylureas 2

Pharmacokinetic Considerations

• The elimination half-life alone may not fully predict the duration of action of sulfonylureas 1
• Sulfonylureas are primarily metabolized by the liver, with metabolites excreted in both urine and bile 6
• Second-generation sulfonylureas like glibenclamide are approximately 200 times more potent than first-generation agents like tolbutamide, due to greater intrinsic hypoglycemic potency rather than prolonged half-life 6
• In patients with MODY (Maturity Onset Diabetes of the Young), the half-life of glipizide remains similar to control subjects (3.8±0.7 vs 3.7±1.8 hours) 3

Dosing Recommendations

• Due to their potency and risk of hypoglycemia, sulfonylureas should be initiated at the lowest possible effective dose 5
• Once-daily administration of a short-acting sulfonylurea in a moderate dose may help avoid desensitization of the insulinotropic effect 5
• In patients with renal impairment, dose adjustments are necessary for most sulfonylureas to avoid prolonged hypoglycemia 2