What are the side effects of glipizide?

Glipizide Side Effects

Hypoglycemia is the most significant side effect of glipizide, particularly in older adults, those with renal impairment, and patients taking multiple medications. 1, 2

Common Side Effects

Hypoglycemia

• Most serious and common adverse effect
• Risk factors:
  • Advanced age (especially >65 years)
  • Renal impairment
  • Polypharmacy (especially with antimicrobials like fluoroquinolones and sulfamethoxazole-trimethoprim) 2
  • Skipped meals
  • Excessive alcohol consumption
  • Concomitant use of other hypoglycemic agents

Gastrointestinal Effects

• Occur in approximately 1 in 70 patients 1
• Include:
  • Nausea
  • Diarrhea
  • Constipation (1 in 100 patients)
  • Gastralgia (1 in 100 patients)
• Generally dose-related and may resolve with dose reduction

Central Nervous System Effects

• Occur in approximately 1 in 50 patients 1
• Include:
  • Dizziness
  • Drowsiness
  • Headache
• Usually transient and rarely require discontinuation

Less Common but Serious Side Effects

Dermatologic Reactions

• Allergic skin reactions (1 in 70 patients) 1
  • Erythema
  • Morbilliform or maculopapular eruptions
  • Urticaria
  • Pruritus
  • Eczema
• Photosensitivity reactions
• Porphyria cutanea tarda

Hematologic Abnormalities

• Rare but potentially serious 1
  • Leukopenia
  • Agranulocytosis
  • Thrombocytopenia
  • Hemolytic anemia
  • Aplastic anemia
  • Pancytopenia

Hepatic Effects

• Cholestatic jaundice (rare)
• Hepatocellular liver injury with jaundice (rare)
• Mild to moderate elevations of liver enzymes (SGOT, LDH, alkaline phosphatase)

Metabolic/Endocrine Effects

• Hyponatremia
• Syndrome of inappropriate antidiuretic hormone (SIADH) secretion
• Weight gain 2

Special Considerations

Renal Impairment

• Glipizide is preferred over other sulfonylureas in patients with chronic kidney disease 3
• Unlike glyburide, glipizide can be used with caution in patients with renal impairment 2
• Conservative initial dosing recommended in renal impairment 2

Cardiovascular Considerations

• May potentially increase cardiovascular mortality 2
• Risk of syncope 2

Elderly Patients

• Higher risk of severe hypoglycemia 4
• Should start with lower doses 2
• Consider reducing or discontinuing if patient experiences persistent gastrointestinal side effects 2

Monitoring Recommendations

1. Monitor blood glucose regularly, especially when initiating therapy
2. Watch for signs of hypoglycemia (confusion, dizziness, sweating, shakiness)
3. Consider periodic liver function tests
4. Monitor renal function in patients with or at risk for kidney disease
5. Be vigilant for drug interactions, especially with antimicrobials

Drug Interactions

• Antimicrobials (especially fluoroquinolones and sulfamethoxazole-trimethoprim) can increase effective sulfonylurea dose and precipitate hypoglycemia 2
• Diuretics and benzodiazepines may increase risk of hypoglycemia 4

Pitfalls and Caveats

• Severe hypoglycemia can occur even with appropriate dosing, especially in elderly patients
• Renal impairment significantly increases hypoglycemia risk (odds ratio 4.0) 4
• Polypharmacy increases risk of adverse effects
• Symptoms of hypoglycemia may be masked in elderly patients or those on beta-blockers
• Discontinue if cholestatic jaundice or other serious adverse effects occur

When prescribing glipizide, always consider the patient's age, renal function, and concomitant medications to minimize the risk of adverse effects, particularly hypoglycemia.