Metformin Use in CKD: eGFR Limits
Metformin is contraindicated when eGFR falls below 30 mL/min/1.73 m², should not be initiated when eGFR is below 45 mL/min/1.73 m², and requires dose reduction and careful monitoring when eGFR is between 30-44 mL/min/1.73 m². 1, 2
eGFR-Based Prescribing Algorithm
eGFR ≥60 mL/min/1.73 m²
- Standard dosing with no adjustment required 1, 3
- Monitor renal function at least annually 1, 4
- Maximum dose up to 2550 mg daily is acceptable 1
eGFR 45-59 mL/min/1.73 m²
- Continue current dose but increase monitoring frequency to every 3-6 months 1, 3
- Consider dose reduction in elderly patients or those with concurrent liver disease 3, 5
- Reassess benefits and risks of continuing therapy 1
- Standard starting doses (500 mg twice daily or 850 mg once daily) are appropriate if initiating therapy 4
eGFR 30-44 mL/min/1.73 m²
- Reduce dose to 50% of maximum (typically 1000 mg daily maximum) 1, 3, 5
- Do not initiate metformin in this range 1, 2
- If already on therapy, continue with reduced dose and monitor every 3-6 months 3, 5
- Starting dose should be 500 mg once daily if continuation is deemed necessary 3
eGFR <30 mL/min/1.73 m²
- Absolute contraindication - discontinue immediately 1, 3, 2
- Substantially increased risk of lactic acidosis 2, 6
- Consider alternative agents: SGLT2 inhibitors (if eGFR ≥20), GLP-1 receptor agonists, DPP-4 inhibitors, or insulin 1, 5
Critical Safety Considerations
Temporary Discontinuation Required
Stop metformin during these high-risk situations: 1, 5, 2
- Iodinated contrast procedures when eGFR is 30-60 mL/min/1.73 m² (restart only after confirming stable renal function at 48 hours) 1, 2
- Surgical procedures with restricted oral intake 2
- Acute illnesses causing volume depletion or hypoxemia 5, 2
- Sepsis, acute heart failure, or cardiovascular collapse 2
"Sick Day Rules" Education
Patients must temporarily stop metformin during: 5
- Severe vomiting or diarrhea
- Dehydration
- Serious intercurrent illness
- Any condition increasing acute kidney injury risk
Monitoring Requirements
Frequency Based on eGFR
- eGFR ≥60: Annual monitoring 4
- eGFR 45-59: Every 3-6 months 1, 3
- eGFR 30-44: Every 3-6 months 1, 3
- Elderly patients: More frequent assessment regardless of baseline eGFR 1, 2
Additional Monitoring
- Vitamin B12 levels in patients on metformin >4 years 3, 5
- Lactate levels if lactic acidosis suspected (symptoms: malaise, myalgias, abdominal pain, respiratory distress, somnolence) 2
Common Pitfalls to Avoid
Dosing Errors
The most critical error is continuing metformin when eGFR drops below 30 mL/min/1.73 m² - this substantially increases lactic acidosis risk and mortality 2, 6. Research shows that approximately 78% of patients with eGFR <30 inappropriately remain on metformin in some practice settings 7.
Contrast Procedures
Failure to hold metformin before contrast imaging in patients with eGFR 30-60 mL/min/1.73 m² can precipitate acute kidney injury and lactic acidosis 1, 2. Always verify eGFR is stable 48 hours post-procedure before restarting 2.
Initiation vs. Continuation
The FDA distinguishes between these scenarios: initiation is not recommended below eGFR 45, but continuation with dose reduction is acceptable down to eGFR 30 1, 2. This reflects the balance between avoiding new exposure in vulnerable patients while recognizing established benefits in those already tolerating therapy 4.
Alternative Agents When Metformin is Contraindicated
When eGFR falls below thresholds for safe metformin use: 1, 5
- SGLT2 inhibitors (dapagliflozin, empagliflozin) for eGFR ≥20-25 mL/min/1.73 m² - provide cardiovascular and renal protection independent of glucose lowering 1
- GLP-1 receptor agonists (semaglutide, dulaglutide, liraglutide) - no dose adjustment needed, reduce cardiovascular events and slow CKD progression 1, 5
- DPP-4 inhibitors with appropriate dose reduction 5
- Insulin - always an option regardless of renal function 5