Glyburide is a second-generation sulfonylurea that stimulates pancreatic insulin secretion.

It is associated with a higher risk of prolonged hypoglycemia compared to other sulfonylureas.

→ Sulfonylureas

Glyburide binds to:

• Sulfonylurea receptor (SUR1)
• Component of the ATP-sensitive potassium (KATP) channel on pancreatic beta cells

Mechanism sequence:

• KATP channel closure
• Membrane depolarization
• Calcium influx
• Insulin release

Important:

• Insulin secretion is NOT glucose-dependent
• Hypoglycemia risk is significant

• Moderate HbA1c reduction
• Weight gain
• Higher risk of hypoglycemia compared to glipizide

Requires functional pancreatic beta cells.

• Longer duration of action
• Hepatic metabolism
• Active metabolites

Because metabolites are active, hypoglycemia may be prolonged — especially in renal impairment.

Common:

• Hypoglycemia
• Weight gain

Severe risk:

• Prolonged hypoglycemia
• Increased risk in elderly
• Increased risk in CKD

Avoid in:

• Elderly patients
• Renal impairment
• History of severe hypoglycemia

Caution in:

• Irregular meal patterns
• Alcohol use

Compared to:

• Glipizide → higher hypoglycemia risk
• Glimepiride → higher hypoglycemia risk

Glipizide is generally preferred in older adults and CKD.

Glyburide has been studied in gestational diabetes.

However, insulin remains the preferred therapy in pregnancy.

Compared to:

• Metformin → more hypoglycemia, more weight gain
• GLP-1 Receptor Agonists → no weight loss, no ASCVD benefit
• SGLT2 Inhibitors → no heart failure benefit

Sulfonylureas are inexpensive but lack cardioprotective benefit.

• Second-generation sulfonylurea
• Active metabolites
• Higher risk of prolonged hypoglycemia
• Avoid in elderly and CKD
• Weight gain common
• Less preferred in modern practice

• Sulfonylureas
• Glipizide
• Glimepiride
• Metformin