What is the recommended dose of glipizide (Glucotrol) for a patient with impaired renal function, specifically an estimated Glomerular Filtration Rate (eGFR) of 30-40?

Glipizide Dosing in eGFR 30-40

For patients with eGFR 30-40 mL/min/1.73 m², initiate glipizide at 2.5 mg daily and titrate cautiously, as this population requires conservative dosing due to increased hypoglycemia risk despite glipizide's primarily hepatic metabolism. 1

Initial Dosing Strategy

• Start with 2.5 mg once daily in patients with eGFR 30-40 mL/min/1.73 m², which is half the standard initial dose used in patients with normal renal function 1
• Avoid long-acting formulations in this population due to elevated hypoglycemia risk 1
• Monitor blood glucose closely during initiation and titration, with reassessment of eGFR at least every 3-6 months 2

Rationale for Conservative Dosing

• Although glipizide is primarily hepatically metabolized, patients with eGFR <50 mL/min/1.73 m² still experience increased hypoglycemia risk 1
• Hospitalized patients with GFR ≤30 mL/min/1.73 m² have a 3.64-fold increased odds of hypoglycemia when treated with sulfonylureas 3
• The National Kidney Foundation recommends glipizide as an option in severe renal impairment specifically because of its hepatic metabolism, but emphasizes careful monitoring 1

Titration and Monitoring

• Titrate upward gradually based on glycemic response, avoiding aggressive dose escalation 1
• Educate patients on hypoglycemia recognition and management, as this is crucial in renal impairment 2
• Increase monitoring frequency if there is rapid eGFR progression, new medication initiation, or change in clinical status 4

Important Clinical Caveats

• Avoid glyburide entirely in patients with any degree of renal impairment, as it is contraindicated due to renal excretion and accumulation risk 1, 2
• Glipizide was associated with lower hypoglycemia rates compared to glyburide in hospitalized patients (16% vs 22%), making it the preferred sulfonylurea in this setting 3
• Patients aged ≥65 years have a 3.07-fold increased odds of hypoglycemia with sulfonylureas, requiring even more conservative dosing in elderly patients with reduced eGFR 3

Alternative Therapeutic Considerations

While glipizide can be used, the KDIGO 2020 guidelines prioritize other agents in this eGFR range:

• SGLT2 inhibitors are recommended (Grade 1A) for patients with T2D and eGFR ≥30 mL/min/1.73 m² due to cardiovascular and kidney benefits 5
• DPP-4 inhibitors may be preferable with lower hypoglycemia risk, though they require dose adjustment (except linagliptin) 1
• GLP-1 receptor agonists (liraglutide, dulaglutide, semaglutide) require no dose adjustment and have lower hypoglycemia risk 1

When to Reduce or Discontinue Sulfonylureas

• If adding an SGLT2 inhibitor to meet cardiovascular or kidney protection goals, consider reducing or discontinuing the sulfonylurea to prevent hypoglycemia 5
• Temporarily discontinue during intercurrent illness to prevent acute kidney injury and medication accumulation 2