Is Oha safe to use in patients with Chronic Kidney Disease (CKD)?

Use of Oral Hypoglycemic Agents (OHAs) in Chronic Kidney Disease (CKD)

The safety of oral hypoglycemic agents in CKD depends on the specific medication and the patient's level of kidney function, with metformin being safe for eGFR ≥30 mL/min/1.73m², while other agents require dose adjustments or may be contraindicated at lower GFR levels. 1

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 1
• Regular monitoring of eGFR, electrolytes, and medication levels is essential when prescribing OHAs to CKD patients 1
• Medication review should be performed periodically and at transitions of care to assess continued indication and potential drug interactions 1
• The risk of adverse drug reactions increases significantly with declining kidney function, with each 1 mL/min/1.73m² lower baseline eGFR associated with higher risk 2

Specific OHA Recommendations Based on eGFR

Metformin

• Can be used safely and effectively when eGFR ≥30 mL/min/1.73m² 1
• Remains the reasonable first-line therapy in patients with CKD as long as eGFR exceeds 30 mL/min/1.73m² 1
• Should be discontinued when eGFR falls below 30 mL/min/1.73m² due to increased risk of lactic acidosis 1

Sulfonylureas

• 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 1
• Long-acting sulfonylureas (e.g., glyburide) should not be used at any level of CKD due to prolonged hypoglycemia risk 1

SGLT-2 Inhibitors

• Current recommendations advise against use when eGFR <30 mL/min/1.73m² 1
• Show promising benefits for heart failure and potential renal protection, but ongoing trials are needed to confirm safety at lower eGFR levels 1

GLP-1 Receptor Agonists

• No dose reduction needed when eGFR >15 mL/min/1.73m² 1
• May help reduce albuminuria levels in patients with type 2 diabetes 3

DPP-4 Inhibitors

• Require dose reduction at lower eGFR levels 1
• Generally well-tolerated in CKD patients with appropriate dose adjustments 1

Insulin

• Safe to use at any level of kidney function 1
• Lower doses are required with impaired renal function 1
• Dose adjustments should be made as kidney function declines 1

Monitoring and Safety Considerations

• Monitor eGFR, electrolytes, and therapeutic medication levels regularly in CKD patients receiving OHAs 1
• Perform thorough medication reviews periodically to assess adherence, continued indication, and potential drug interactions 1
• Patients with CKD often have complex medication regimens and are seen by multiple specialists, increasing the risk of medication errors 1, 2
• Over 27% of serious adverse drug reactions in CKD patients are preventable or potentially preventable 2
• Consider and adapt drug dosing in people where GFR is not in a steady state 1

Special Considerations

• Review and limit the use of over-the-counter medicines and dietary or herbal supplements that may be harmful for people with CKD 1, 4
• Be aware that patients with CKD are at increased risk of orthostatic hypotension, especially when taking multiple antihypertensives alongside diabetes medications 5
• Consider the impact of polypharmacy, as CKD patients often take multiple medications that can interact with OHAs 1, 2
• If medications are discontinued during acute illness, communicate a clear plan of when to restart them 1

Conclusion

When prescribing OHAs in CKD patients, medication choice should be guided by the level of kidney function, with metformin remaining first-line therapy for eGFR ≥30 mL/min/1.73m². Regular monitoring of kidney function and appropriate dose adjustments are essential to minimize adverse effects while maintaining glycemic control.