Metformin Dosing in Chronic Kidney Disease
Metformin is contraindicated in patients with an eGFR below 30 mL/min/1.73 m², but can be used with appropriate dose adjustments in patients with eGFR ≥30 mL/min/1.73 m². 1, 2, 3
Metformin Dosing Based on Kidney Function
| eGFR (mL/min/1.73 m²) | Recommendation | Monitoring Frequency |
|---|---|---|
| ≥60 | Standard dosing (up to 2550 mg/day) | At least annually |
| 45-59 | Consider dose reduction; for some patients | Every 3-6 months |
| 30-44 | Reduce dose by 50% (maximum 1000 mg daily) | Every 3-6 months |
| <30 | Contraindicated - discontinue or do not initiate | N/A |
Initial Dosing and Titration
- Starting dose: 500 mg twice daily or 850 mg once daily with meals
- Titration: Increase by 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability
- Maximum dose:
- Normal kidney function: 2550 mg daily
- eGFR 30-44 mL/min/1.73 m²: 1000 mg daily (50% reduction)
Special Considerations
When to Discontinue Metformin
- eGFR falls below 30 mL/min/1.73 m² 2, 1
- During acute illness with risk of dehydration
- Before iodinated contrast imaging procedures in patients with:
- eGFR 30-60 mL/min/1.73 m²
- History of liver disease, alcoholism, or heart failure
- Scheduled for intra-arterial iodinated contrast 1
When to Resume After Contrast
- Re-evaluate eGFR 48 hours after imaging procedure
- Restart metformin only if renal function is stable 1
Risk Factors for Lactic Acidosis
While metformin-associated lactic acidosis is rare, risk increases with:
- Acute kidney injury
- Hypoxemia
- Sepsis
- Alcohol abuse
- Liver failure
- Myocardial infarction
- Shock 4
Monitoring Recommendations
- Kidney function:
- eGFR ≥60: At least annually
- eGFR <60: Every 3-6 months 3
- Vitamin B12: Monitor for deficiency in patients on long-term metformin (>4 years) 2
Combination Therapy
For patients with T2D and CKD with eGFR ≥30 mL/min/1.73 m², consider combination therapy with:
Clinical Pearls
- Despite historical concerns, evidence now supports metformin use in moderate CKD (eGFR 30-59 mL/min/1.73 m²) with appropriate dose adjustments 3, 5
- Metformin offers cardiovascular benefits and may reduce mortality in patients with T2D and CKD 5, 6
- The risk of lactic acidosis with properly dosed metformin is significantly lower than previously thought 7
- Avoid initiating metformin in patients with eGFR between 30-45 mL/min/1.73 m² unless benefits clearly outweigh risks 1