What is the recommended dosing for metformin (biguanide) in a patient with type 2 diabetes mellitus and potential impaired renal function?

Metformin Dosing in Type 2 Diabetes with Impaired Renal Function

Initiate metformin at standard doses (500 mg twice daily or 850 mg once daily) only when eGFR is ≥45 mL/min/1.73 m², reduce the dose to half the maximum when eGFR is 30-44 mL/min/1.73 m², and discontinue completely when eGFR falls below 30 mL/min/1.73 m². 1, 2, 3

eGFR-Based Dosing Algorithm

eGFR ≥60 mL/min/1.73 m²

• Immediate-release formulation: Start 500 mg twice daily or 850 mg once daily with meals 1, 3
• Extended-release formulation: Start 500 mg once daily with the evening meal 1, 2
• Titrate upward by 500 mg weekly or 850 mg every 2 weeks based on glycemic response, up to maximum 2550 mg/day for immediate-release or 2000 mg/day for extended-release 1, 3
• Monitor eGFR at least annually 1, 2

eGFR 45-59 mL/min/1.73 m²

• For new initiation: Start at half the standard dose (250-500 mg once daily) and titrate to half the maximum recommended dose 1, 4
• For patients already on metformin: Continue current dose but consider dose reduction in elderly patients, those with liver disease, or other risk factors for lactic acidosis 1, 4
• Monitor eGFR every 3-6 months 1, 2, 4

eGFR 30-44 mL/min/1.73 m²

• For new initiation: Initiation is NOT recommended at this level of renal function 2, 3
• For patients already on metformin: Reduce dose to half the maximum recommended dose (typically 500-1000 mg daily maximum) 1, 4
• Monitor eGFR every 3-6 months 1, 4
• Assess benefit-risk ratio of continuing therapy 3

eGFR <30 mL/min/1.73 m²

• Absolute contraindication: Stop metformin immediately and do not initiate 1, 2, 5, 3
• This is a hard stop due to risk of lactic acidosis 5, 3

Critical Safety Considerations

Temporary Discontinuation Required

Discontinue metformin in the following situations to prevent lactic acidosis:

• Iodinated contrast procedures when eGFR is 30-60 mL/min/1.73 m², or in patients with liver disease, alcoholism, or heart failure 3
• Surgical procedures with restricted oral intake 2
• Acute illnesses that increase risk of acute kidney injury (implement "sick day rules") 2, 4
• Re-evaluate eGFR 48 hours after contrast procedures before restarting 3

Long-Term Monitoring

• Vitamin B12 deficiency: Monitor patients on metformin for more than 4 years 1, 4
• Renal function: Increase monitoring frequency to every 3-6 months when eGFR <60 mL/min/1.73 m² 1, 2, 4

Combination Therapy Considerations

When metformin alone is insufficient or contraindicated:

• eGFR ≥30 mL/min/1.73 m²: Add an SGLT2 inhibitor as first-line combination therapy (Grade 1A recommendation) 1, 5
• eGFR <30 mL/min/1.73 m²: Consider GLP-1 receptor agonists (preferred), DPP-4 inhibitors, insulin, sulfonylureas, TZDs, or alpha-glucosidase inhibitors 1, 2, 4
• Most patients with eGFR ≥30 mL/min/1.73 m² benefit from both metformin and an SGLT2 inhibitor 1

Common Pitfalls to Avoid

• Do not continue metformin at any dose when eGFR <30 mL/min/1.73 m² - this is an absolute contraindication regardless of prior tolerance 5, 3
• Do not initiate metformin when eGFR is 30-44 mL/min/1.73 m² - the FDA and guidelines recommend against new starts in this range 2, 3
• Do not forget to reassess eGFR with any significant clinical change - acute illness, dehydration, or new nephrotoxic medications require immediate renal function evaluation 4
• Do not overlook the need for dose reduction at eGFR 30-44 mL/min/1.73 m² - continuing full doses increases lactic acidosis risk 1, 4