From the Guidelines
Oral hypoglycemic agents (OHAs) such as metformin, sulfonylureas like glyburide, and SGLT2 inhibitors should be avoided or used with caution in patients with chronic kidney disease (CKD), with specific considerations based on the patient's eGFR level and individualized glycemic targets. According to the most recent evidence from 1, several OHAs have specific dosing recommendations and considerations in patients with CKD.
- Metformin should be avoided in advanced CKD (eGFR <30 ml/min/1.73m²) due to increased risk of lactic acidosis, though it can be used with dose reduction when eGFR is 30-45 ml/min/1.73m².
- Sulfonylureas like glyburide should be avoided in CKD as they are primarily eliminated by the kidneys and can cause prolonged hypoglycemia; glipizide is preferred if a sulfonylurea is needed.
- SGLT2 inhibitors generally have reduced efficacy in advanced CKD and most should not be initiated when eGFR is below 45 ml/min/1.73m², though some newer agents like empagliflozin and canagliflozin have expanded indications for renoprotection.
- GLP-1 receptor agonists like exenatide should be avoided in severe CKD, while others like liraglutide and dulaglutide may be used with caution.
- DPP-4 inhibitors are generally safer in CKD but may require dose adjustments, as recommended for sitagliptin, saxagliptin, and alogliptin 1. The kidneys' reduced ability to clear medications and their metabolites in CKD patients increases the risk of drug accumulation and adverse effects, making appropriate medication selection and dosing crucial for these patients. Key considerations for OHA use in CKD include:
- Monitoring eGFR levels and adjusting medication doses accordingly
- Avoiding medications with high risk of hypoglycemia or lactic acidosis
- Using medications with established cardiovascular and renoprotective benefits, such as SGLT2 inhibitors and GLP-1 receptor agonists
- Individualizing glycemic targets and medication regimens based on patient-specific factors, such as comorbidities and medication tolerance.
From the Research
Oral Hypoglycemic Agents (OHAs) to Avoid in CKD
The following OHAs should be avoided or used with caution in patients with Chronic Kidney Disease (CKD):
- Sulfonylurea (SU) due to the risk of prolonged hypoglycemia 2
- Metformin in patients with moderate to advanced CKD, although recent studies suggest that metformin may be safe to use in mild to moderate CKD 3, 4, 5
- Alpha-glucosidase inhibitors in patients with advanced stage CKD and on dialysis, as recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines 2
Special Considerations
- Metformin use is associated with an increased risk of lactic acidosis at eGFR less than 30 mL/min/1.73 m2 5
- Metformin should be discontinued if renal function falls below an eGFR of 30 mL/min/1.73 m2 or during acute renal deterioration 4
- Patients with CKD should be aware of the potential risks of lactic acidosis and the importance of preventing drug accumulation by discontinuing metformin in certain situations, such as sepsis, fever, diarrhea, or vomiting 6
Alternative Therapies
- Insulin injection therapy remains the mainstay of treatment in diabetic patients with moderate to advanced CKD, particularly in those receiving dialysis therapy 2
- Repaglinide and mitiglinide are rapid- and short-acting insulinotropic SU receptor ligands that may be attractive therapeutic options for patients with CKD 2
- Dipeptidyl peptidase-4 inhibitors and incretin mimetics are new antihyperglycemic agents that may be used more frequently in the future in patients with type 2 diabetes and CKD 2