Can Glipizide (Glipizide) be used in patients with Chronic Kidney Disease (CKD) stage 4, characterized by Impaired Renal Function?

From the Guidelines

Glipizide can be used cautiously in CKD stage 4, as it is the preferred second-generation sulfonylurea due to its lack of active metabolites, but dose adjustment and close monitoring are necessary to avoid hypoglycemia. According to the 2012 KDOQI clinical practice guideline for diabetes and CKD 1, glipizide is the preferred agent among second-generation sulfonylureas for patients with CKD because it does not have active metabolites, reducing the risk of hypoglycemia. However, patients with CKD stage 4 are at increased risk of hypoglycemia due to decreased clearance of insulin and oral agents, as well as impaired renal gluconeogenesis.

Key Considerations

• The risk of hypoglycemia is increased in patients with substantial decreases in eGFR, such as those with CKD stages 4 and 5 1.
• Glipizide is primarily metabolized by the liver, with inactive metabolites excreted by the kidneys, making it a safer option than other sulfonylureas with active metabolites requiring renal clearance.
• Dose adjustment is necessary, typically starting at a lower dose of 2.5 mg daily and carefully titrating based on blood glucose response.
• Close monitoring of blood glucose levels is essential, especially during dose adjustments, to minimize the risk of hypoglycemia.
• Alternative medications like DPP-4 inhibitors or certain GLP-1 receptor agonists may be safer options for patients with CKD stage 4, as suggested by the 2019 American Heart Association and Heart Failure Society of America statement 1.

Monitoring and Dose Adjustment

• Blood glucose should be checked frequently, especially during dose adjustments, to avoid hypoglycemia.
• Patients should be educated on the signs and symptoms of hypoglycemia and how to manage it.
• The dose of glipizide should be adjusted based on blood glucose response, and alternative medications should be considered if the patient experiences hypoglycemia or if the dose needs to be significantly reduced.

From the FDA Drug Label

Renal and Hepatic Disease:The metabolism and excretion of glipizide may be slowed in patients with impaired renal and/or hepatic function If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.

• The FDA drug label does mention that glipizide metabolism and excretion may be slowed in patients with impaired renal function, which includes CKD stage 4.
• However, it does not provide explicit guidance on the use of glipizide in patients with CKD stage 4.
• Given the potential for prolonged hypoglycemia in patients with impaired renal function, caution should be exercised when using glipizide in patients with CKD stage 4 2 2.
• A conservative approach to dosing and monitoring may be necessary to minimize the risk of hypoglycemia.

From the Research

Glipizide Use in CKD Stage 4

• The use of glipizide in patients with chronic kidney disease (CKD) stage 4 is a topic of interest due to the potential risks of hypoglycemia and the need for careful management of blood glucose levels in this population.
• According to a study published in 2017 3, noninsulin antidiabetes agents like glipizide may be used in patients with end-stage renal disease (ESRD) in appropriate doses to decrease the risk of hypoglycemia.
• Another study from 2003 4 suggests that glipizide may be associated with a lower risk of hypoglycemia compared to other sulfonylureas like glibenclamide, and may be beneficial in individuals with renal impairment.
• A retrospective cohort study from 2018 5 found that glipizide was associated with a higher risk of serious hypoglycemia compared to metformin, but a lower risk compared to other sulfonylureas like glyburide and glimepiride.

Considerations for Glipizide Use in CKD Stage 4

• Patients with CKD stage 4 are at high risk for hypoglycemia due to impaired insulin clearance and changes in glucose metabolism 3.
• The use of glipizide in this population requires careful monitoring of blood glucose levels and adjustment of doses to minimize the risk of hypoglycemia.
• Alternative antidiabetic agents like dipeptidyl peptidase-4 inhibitors and repaglinide may also be considered in patients with CKD stage 4, as they may be associated with a lower risk of hypoglycemia 3.