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

It is one of the most commonly used sulfonylureas.

→ Sulfonylureas

Glipizide binds to:

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

Mechanism sequence:

• Closure of KATP channel
• Membrane depolarization
• Opening of voltage-gated calcium channels
• Increased intracellular calcium
• Insulin release

Important:

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

• Moderate HbA1c reduction
• Rapid onset of action
• Weight gain
• Risk of hypoglycemia

Requires functional pancreatic beta cells.

• Shorter half-life than glyburide
• Available in immediate-release and extended-release formulations
• Primarily metabolized in the liver
• Inactive metabolites

Glipizide is preferred over glyburide in patients with renal impairment due to lower hypoglycemia risk.

Common:

• Hypoglycemia
• Weight gain

Severe hypoglycemia risk increases with:

• Elderly patients
• Renal impairment
• Irregular meal intake
• Alcohol use

• Type 1 Diabetes
• History of severe hypoglycemia
• Caution in elderly
• Caution in CKD

Compared to:

• Glyburide → lower hypoglycemia risk
• Glimepiride → similar efficacy

Glipizide is generally preferred over glyburide in older adults.

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 effects.

• Second-generation sulfonylurea
• Closes beta-cell KATP channels
• Hypoglycemia risk
• Weight gain
• Preferred over glyburide in CKD
• Requires functioning beta cells

• Sulfonylureas
• Glyburide
• Glimepiride
• Metformin