Does metformin affect kidney function?

Metformin's Effects on Kidney Function

Metformin is primarily cleared by the kidneys and requires dose adjustment or discontinuation based on kidney function, with accumulation in renal impairment potentially leading to lactic acidosis, though this risk is lower than historically believed. 1, 2

Metformin Clearance and Kidney Function

Metformin is substantially excreted by the kidneys, making kidney function a critical consideration when prescribing this medication:

• Metformin clearance decreases by approximately 75% when GFR falls to 60 mL/min/1.73 m² 1
• Despite this reduction in clearance, serum metformin concentrations typically remain only about two-fold higher than in patients with normal kidney function 1
• These elevated levels represent only about 3% of concentrations found in cases of true metformin-associated lactic acidosis 1

Risk of Lactic Acidosis

The primary concern with metformin use in kidney disease is lactic acidosis, though evidence suggests this risk is lower than historically believed:

• Lactic acidosis is a rare but serious side effect characterized by elevated blood lactate (>5 mmol/L), anion gap acidosis, and increased lactate:pyruvate ratio 2
• The incidence of lactic acidosis in metformin users ranges from approximately 3-10 per 100,000 person-years, generally indistinguishable from background rates in the diabetic population 3
• In studies of patients with GFR levels between 30-60 mL/min/1.73 m², lactic acidosis remained exceedingly rare even with comorbid conditions like heart failure, COPD, and liver disease 1

Current Recommendations for Metformin Use Based on Kidney Function

Guidelines have evolved to allow more liberal use of metformin in mild-to-moderate kidney disease:

• FDA label contraindications: Metformin is contraindicated in patients with eGFR <30 mL/min/1.73 m² 2
• Dose adjustments:
  • eGFR 45-59 mL/min/1.73 m²: No dose adjustment needed in most patients
  • eGFR 30-44 mL/min/1.73 m²: Reduce dose to 50% (e.g., 250 mg twice daily instead of 500 mg twice daily) 4
  • eGFR <30 mL/min/1.73 m²: Discontinue metformin 1, 2

Monitoring Recommendations

For patients taking metformin with impaired kidney function:

• Monitor eGFR at least annually in all patients taking metformin 2
• More frequent monitoring (every 3-6 months) for those with moderate renal impairment 4
• Temporarily discontinue metformin during acute illness, surgery, or procedures with contrast media that may affect kidney function 2
• Monitor for vitamin B12 deficiency in patients on long-term metformin therapy (>4 years) 1, 4

Special Considerations

• Sick day rules: Patients should be advised to stop metformin during acute illness, surgery, or other situations that may lead to dehydration or acute kidney injury 1
• Contrast studies: Metformin should be stopped at the time of or prior to iodinated contrast procedures in patients with eGFR between 30-60 mL/min/1.73 m² and restarted 48 hours after if renal function remains stable 2
• Elderly patients: Require more careful monitoring due to age-related decline in kidney function 2

Clinical Benefits Despite Renal Concerns

Despite renal concerns, metformin offers significant benefits that should be considered:

• Cardiovascular protection and reduced mortality risk even in patients with mild-to-moderate kidney disease 1, 5
• Weight neutrality or weight loss benefits 6
• Improvement in components of metabolic syndrome 6
• Low risk of hypoglycemia compared to other diabetes medications 1

The evidence supports cautious use of metformin in patients with mild to moderate chronic kidney disease with appropriate dose adjustments and careful monitoring of kidney function.