Examples of Sulfonylureas
Sulfonylureas are divided into first-generation and second-generation agents, with the second-generation drugs—glipizide, glyburide (glibenclamide), glimepiride, and gliclazide—being the most commonly used in current clinical practice. 1, 2, 3
Second-Generation Sulfonylureas (Preferred)
The following are the primary sulfonylureas used in contemporary type 2 diabetes management:
Glipizide - A short-acting agent with a half-life of 2-7 hours, preferred in elderly patients and those with renal impairment due to its lack of active metabolites 1, 4, 5
Glyburide (Glibenclamide) - A longer-acting agent with a half-life of 7-10 hours, though it carries the highest risk of hypoglycemia among second-generation agents and should be avoided in elderly patients 1, 5, 3
Glimepiride - A once-daily agent (1-8 mg/day dosing range) with lower hypoglycemia risk than glyburide and potential preservation of cardioprotective responses to ischemia 1, 6, 2
Gliclazide (Gliclazide MR) - Another second-generation agent with lower hypoglycemia risk, particularly useful during fasting periods 1, 3
First-Generation Sulfonylureas (Generally Avoided)
These older agents should generally be avoided due to prolonged half-lives and increased hypoglycemia risk:
Chlorpropamide - Associated with substantially higher hypoglycemia risk than second-generation agents 1, 5
Tolbutamide - An older agent with less favorable safety profile 5, 7
Tolazamide - Another first-generation agent rarely used in contemporary practice 5
Key Clinical Distinctions
The American Diabetes Association recommends glimepiride and glipizide over glyburide due to their lower hypoglycemia risk, with glipizide being the preferred agent in patients with renal impairment because it lacks active metabolites that accumulate 1. Glyburide is explicitly contraindicated in elderly patients by the American Geriatrics Society due to prolonged hypoglycemia risk 1.
All sulfonylureas work by stimulating insulin secretion from pancreatic β-cells and are capable of reducing HbA1c by approximately 1.5 percentage points 1, 2, 3. However, they all carry risk of hypoglycemia and weight gain (approximately 2 kg), with the magnitude varying by specific agent 1, 7.