Should metformin be stopped in patients with impaired renal function, specifically a Glomerular Filtration Rate (GFR) under 30?

Metformin Use in Patients with eGFR <30 mL/min/1.73 m²

Metformin should be discontinued when eGFR falls below 30 mL/min/1.73 m² due to increased risk of metformin-associated lactic acidosis. 1, 2

Rationale for Discontinuation

• Metformin is substantially excreted by the kidneys, and its clearance is proportional to GFR, leading to drug accumulation in severe renal impairment 1
• The FDA explicitly contraindicates metformin in patients with an eGFR below 30 mL/min/1.73 m² 2
• KDIGO 2020 guidelines clearly recommend stopping metformin when eGFR falls below 30 mL/min/1.73 m² 1
• The risk of metformin-associated lactic acidosis increases significantly with severe renal impairment (eGFR <30) 3, 4

Dosing Recommendations Based on Renal Function

• For eGFR ≥45 mL/min/1.73 m²: Standard dosing with regular monitoring 1, 3
• For eGFR 30-44 mL/min/1.73 m²: Reduce dose to maximum 1000 mg daily (half the maximum dose) 1, 3
• For eGFR <30 mL/min/1.73 m²: Discontinue metformin completely 1, 2

Monitoring Recommendations

• Monitor eGFR at least every 3-6 months in patients with eGFR <60 mL/min/1.73 m² 1, 3
• Increase monitoring frequency during periods of illness or when starting medications that may affect kidney function 1, 3
• Assess for symptoms of lactic acidosis (nausea, vomiting, abdominal pain, muscle cramps, general malaise) 2

Temporary Discontinuation ("Sick Day Rules")

• Temporarily discontinue metformin during:
  • Serious intercurrent illness 1, 3
  • Procedures involving iodinated contrast agents 2
  • Surgery or angiography 3
  • Acute illness at home that may affect hydration or kidney function 1, 3

Alternative Medications When eGFR <30 mL/min/1.73 m²

• Consider GLP-1 receptor agonists or DPP-4 inhibitors with appropriate renal dose adjustments 1, 3
• Insulin therapy may be required for adequate glycemic control 1
• SGLT2 inhibitors are generally not recommended in advanced kidney disease 1

Evidence Quality and Considerations

• The recommendation to discontinue metformin at eGFR <30 mL/min/1.73 m² is consistent across multiple high-quality guidelines 1, 3
• The FDA drug label explicitly contraindicates metformin in patients with eGFR <30 mL/min/1.73 m² 2
• While some observational studies suggest metformin might be safe in more advanced CKD 5, 6, there are documented cases of lactic acidosis in patients with severe renal impairment 7
• The risk-benefit ratio strongly favors discontinuation at this level of kidney function 3, 4

Common Pitfalls to Avoid

• Failing to monitor renal function regularly in patients on metformin 3
• Not adjusting metformin dose when eGFR falls below 45 mL/min/1.73 m² 1, 3
• Continuing metformin during acute illness or procedures that may cause acute kidney injury 1, 2
• Not educating patients about "sick day rules" for temporary metformin discontinuation 1, 3