What are the contraindications for glipizide (a sulfonylurea)?

Glipizide Contraindications

Glipizide is absolutely contraindicated in patients with known hypersensitivity to the drug, type 1 diabetes mellitus, and diabetic ketoacidosis (with or without coma). 1

Absolute Contraindications

The FDA drug label explicitly identifies three absolute contraindications for glipizide:

• Known hypersensitivity to glipizide or other sulfonylureas 1
• Type 1 diabetes mellitus - these patients require insulin therapy 1
• Diabetic ketoacidosis (with or without coma) - this condition must be treated with insulin, not oral agents 1

Strong Relative Contraindications (Use Not Recommended)

Severe Renal Impairment

• Glyburide (not glipizide) is explicitly not recommended in patients with chronic kidney disease 2
• However, glipizide requires conservative initiation (e.g., 2.5 mg once daily) and slow titration in patients with any degree of renal impairment to avoid hypoglycemia 2
• Glipizide is actually the preferred sulfonylurea in renal impairment because it lacks active metabolites that accumulate 3

Significant Hepatic Disease

• Glipizide is contraindicated in patients with significant liver disease due to altered drug metabolism and increased hypoglycemia risk 4

Heart Failure and High Cardiovascular Risk

• Patients with established heart failure should NOT receive glipizide - observational studies show sulfonylureas are associated with greater mortality risk than metformin in heart failure patients 5
• The American Heart Association and American College of Cardiology strongly prefer metformin and SGLT-2 inhibitors over sulfonylureas in patients at high cardiovascular risk 5

Clinical Situations Requiring Extreme Caution

Elderly Patients

• While not contraindicated, elderly patients have substantially higher risk of severe, prolonged hypoglycemia with all sulfonylureas 3
• The American Geriatrics Society explicitly contraindicates glyburide (not glipizide) in elderly patients, but recommends glipizide be used with careful dose selection if a sulfonylurea is necessary 3

Prolonged Fasting States

• Use with extreme caution during Ramadan or other prolonged fasting - patients must break the fast immediately if blood glucose drops below 60-70 mg/dL 5
• For twice-daily dosing during fasting: use half the usual morning dose at predawn meal and full dose at sunset meal 5

Irregular Eating Patterns

• Patients who skip or delay meals are at significantly higher risk of hypoglycemia and may not be suitable candidates for glipizide 5

Perioperative Period

• Consider temporary discontinuation during major surgery and switch to insulin during the perioperative period 5

Common Pitfalls to Avoid

• Do not use glipizide as first-line therapy in patients with established cardiovascular disease, heart failure, or chronic kidney disease - SGLT-2 inhibitors and GLP-1 receptor agonists are strongly preferred 5, 6
• Beware of drug interactions: Fluoroquinolones and sulfamethoxazole-trimethoprim increase effective glipizide dose and may precipitate hypoglycemia - consider temporary dose reduction or discontinuation 3
• Never use in hospital settings routinely - professional societies recommend against routine inpatient use due to potential for sustained hypoglycemia 3
• When combining with DPP-4 inhibitors, hypoglycemia risk increases by approximately 50% - consider sulfonylurea dose reduction 3, 6

Key Distinction from Other Sulfonylureas

Unlike glyburide, which is explicitly contraindicated in elderly patients and those with renal impairment, glipizide can be used cautiously in these populations because it lacks active metabolites and has a shorter duration of action 2, 3. However, it still requires conservative initiation at 2.5 mg once daily and slow titration 2.