Use of Oral Hypoglycemic Agents in Chronic Kidney Disease

General Principles for OHA Use in CKD

• Patients with CKD are more susceptible to medication-related adverse effects due to altered pharmacokinetics and reduced drug clearance, highlighting the need for careful medication management in this population, as recommended by the Kidney International guidelines 3
• Regular monitoring of eGFR, electrolytes, and medication levels is essential when prescribing OHAs to CKD patients to minimize the risk of adverse effects, according to the Kidney International guidelines 3
• Medication review should be performed periodically and at transitions of care to assess continued indication and potential drug interactions in CKD patients, as advised by the Kidney International guidelines 3

Specific OHA Recommendations Based on eGFR

• The American Heart Association recommends that metformin can be used safely and effectively when eGFR ≥30 mL/min/1.73m², with a moderate level of evidence supporting its use in this population 1, 2
• The American College of Cardiology recommends that metformin remains the reasonable first-line therapy in patients with CKD as long as eGFR exceeds 30 mL/min/1.73m², based on high-quality evidence 1, 2
• The American Diabetes Association advises that metformin should be discontinued when eGFR falls below 30 mL/min/1.73m² due to increased risk of lactic acidosis, with a strong level of evidence supporting this recommendation 1
• Short-acting sulfonylureas (e.g., glipizide, glimepiride) can be used with caution at reduced doses when eGFR <30 mL/min/1.73m² due to increased hypoglycemia risk, as recommended by the American Heart Association with a low level of evidence 1, 2
• Long-acting sulfonylureas (e.g., glyburide) should not be used at any level of CKD due to prolonged hypoglycemia risk, according to the American College of Cardiology with a moderate level of evidence 1
• Current recommendations from the American Heart Association advise against the use of SGLT-2 inhibitors when eGFR <30 mL/min/1.73m², with ongoing trials needed to confirm safety at lower eGFR levels and a low level of evidence supporting this recommendation 1, 2
• GLP-1 receptor agonists require no dose reduction when eGFR >15 mL/min/1.73m², as recommended by the American Diabetes Association with a moderate level of evidence 1
• DPP-4 inhibitors require dose reduction at lower eGFR levels, with generally well-tolerated use in CKD patients with appropriate dose adjustments, as advised by the American College of Cardiology with a low level of evidence 1
• Insulin is safe to use at any level of kidney function, with lower doses required with impaired renal function and dose adjustments needed as kidney function declines, according to the American Diabetes Association with a high level of evidence 1, 2

Monitoring and Safety Considerations

• The Kidney International guidelines recommend monitoring eGFR, electrolytes, and therapeutic medication levels regularly in CKD patients receiving OHAs to minimize the risk of adverse effects 3
• Regular medication reviews should be performed to assess adherence, continued indication, and potential drug interactions in CKD patients, as advised by the Kidney International guidelines with a moderate level of evidence 3
• Consider and adapt drug dosing in people where GFR is not in a steady state, as recommended by the Kidney International guidelines with a low level of evidence 3

Special Considerations

• The Kidney International guidelines recommend reviewing and limiting the use of over-the-counter medicines and dietary or herbal supplements that may be harmful for people with CKD, with a moderate level of evidence supporting this recommendation 3
• Consider the impact of polypharmacy, as CKD patients often take multiple medications that can interact with OHAs, as advised by the Kidney International guidelines with a low level of evidence 3
• If medications are discontinued during acute illness, communicate a clear plan of when to restart them, as recommended by the Kidney International guidelines with a moderate level of evidence 3