Metformin Renal Dosing
Metformin can be safely used in patients with eGFR ≥30 mL/min/1.73 m² with mandatory dose adjustments, but must be discontinued when eGFR falls below 30 mL/min/1.73 m². 1, 2
eGFR-Based Dosing Algorithm
eGFR ≥60 mL/min/1.73 m²
- Use standard dosing up to maximum 2550 mg daily in divided doses 2
- Monitor eGFR at least annually 1
- No dose adjustment required 3
eGFR 45-59 mL/min/1.73 m²
- Continue current dose without reduction 1, 3
- Increase monitoring frequency to every 3-6 months 1, 3
- Consider dose reduction in patients with additional risk factors: advanced age, liver disease, heart failure, or alcoholism 1, 3
eGFR 30-44 mL/min/1.73 m²
- Mandatory dose reduction to maximum 1000 mg daily (half the maximum recommended dose) 1, 3
- Do not initiate metformin in treatment-naïve patients in this range 2
- If already on metformin when eGFR falls into this range, reduce dose and assess benefit-risk of continuing 2
- Monitor eGFR every 3-6 months 1, 3
eGFR <30 mL/min/1.73 m²
- Absolute contraindication—discontinue metformin immediately 1, 4, 3, 2
- Risk of lactic acidosis and increased all-cause mortality at this level of renal function 4, 5
- Transition to insulin or other appropriate glucose-lowering agents 4
Critical Safety Considerations
Temporary Discontinuation Required
Stop metformin during high-risk situations that increase acute kidney injury risk 1:
- Surgical procedures with restricted oral intake 1
- Acute illnesses causing dehydration, sepsis, or hypoperfusion 1
- Iodinated contrast procedures in patients with eGFR 30-60 mL/min/1.73 m², or those with liver disease, alcoholism, or heart failure 2
- Re-evaluate eGFR 48 hours after contrast procedures before restarting 1, 2
Monitoring Requirements Beyond Renal Function
- Check vitamin B12 levels if on metformin >4 years due to risk of deficiency 1, 3
- More frequent renal monitoring in elderly patients who have higher risk of declining kidney function 2
Evidence Quality and Nuances
The current guidelines from KDIGO and ADA represent a significant liberalization from older restrictions 1. A Cochrane meta-analysis found zero cases of lactic acidosis in metformin users, and real-world data showed metformin reduced all-cause mortality and end-stage renal disease progression in CKD stage 3B 1. Large-scale cohort studies support safe use in mild to moderate renal impairment (eGFR 30-60 mL/min/1.73 m²) 6, 7.
However, one critical study showed increased mortality risk in patients with serum creatinine >530 μmol/L (approximately eGFR <10 mL/min/1.73 m²), with adjusted hazard ratio of 1.35 for all-cause mortality 5. This reinforces the absolute contraindication below eGFR 30 mL/min/1.73 m².
Common Pitfalls to Avoid
- Do not continue metformin "because the patient has been on it for years" when eGFR drops below 30—this significantly increases mortality risk 5
- Do not forget to hold metformin during acute illness—even patients with normal baseline renal function can develop acute kidney injury and subsequent lactic acidosis 8, 9
- Do not assume all patients with eGFR 30-44 can tolerate 1000 mg daily—elderly patients with multiple comorbidities may need lower doses 3
- Renal function can deteriorate rapidly in elderly patients—check eGFR every 3-6 months, not annually, when eGFR <60 1, 3