Metformin Use in Chronic Kidney Disease
Metformin can be safely used in patients with CKD who have an eGFR ≥30 ml/min per 1.73 m², with appropriate dose adjustments based on kidney function. 1
Recommendations Based on eGFR
eGFR ≥60 ml/min per 1.73 m²
eGFR 45-59 ml/min per 1.73 m²
- Continue metformin at current dose 1, 2
- Consider dose reduction in patients with additional risk factors for lactic acidosis (advanced age, liver disease) 1, 2
- Increase monitoring of kidney function to every 3-6 months 1
eGFR 30-44 ml/min per 1.73 m²
- Reduce metformin dose to half the maximum recommended dose (typically 1000 mg daily) 1
- Monitor kidney function every 3-6 months 1
- Monitor for vitamin B12 deficiency, especially if treatment duration exceeds 4 years 1
eGFR <30 ml/min per 1.73 m²
- Discontinue metformin 1
- Do not initiate metformin 1, 3
- Consider alternative glucose-lowering medications appropriate for advanced CKD 1
Risk of Lactic Acidosis
- The risk of metformin-associated lactic acidosis is rare, with an estimated upper limit of 8-10 cases per 100,000 patient-years 4, 5
- Risk increases with declining kidney function, particularly when eGFR falls below 30 ml/min/1.73 m² 3, 6
- Most cases of lactic acidosis occur in the setting of acute illness or conditions causing hypoperfusion and hypoxemia 3, 1
- Temporary discontinuation of metformin is recommended during:
Special Considerations
- Kidney transplant recipients with T2D and eGFR ≥30 ml/min/1.73 m² can be treated with metformin following the same recommendations as other CKD patients 1
- Avoid excessive alcohol intake in patients taking metformin, as alcohol potentiates metformin's effect on lactate metabolism 3
- Metformin should be used cautiously in patients with hepatic impairment due to impaired lactate clearance 3
- Monitor vitamin B12 levels in patients on long-term metformin therapy (>4 years) 1, 2
Combination Therapy
- For most patients with T2D, CKD, and eGFR ≥30 ml/min/1.73 m², combination therapy with metformin and an SGLT2i is beneficial 1
- If glycemic targets are not achieved with metformin and SGLT2i, or if these medications cannot be used, consider adding a GLP-1 receptor agonist 1
Clinical Benefits vs. Risks
- Despite historical concerns, recent evidence supports the safe use of metformin in mild to moderate CKD (eGFR 30-60 ml/min/1.73 m²) with appropriate dose adjustments 6, 5
- Observational studies suggest potential benefits of metformin on cardiovascular outcomes and mortality in CKD patients 7, 5
- Some studies indicate metformin use in CKD may be associated with lower risk of progression to end-stage renal disease 7
By following these evidence-based guidelines for metformin use in CKD, clinicians can maximize the benefits of this first-line diabetes medication while minimizing risks in patients with impaired kidney function.