Metformin Starting Dose in Patients with Impaired Renal Function
For patients with impaired renal function, the recommended starting dose of metformin is 500 mg once daily for immediate-release formulations or 500 mg once daily for extended-release formulations, with dose adjustments based on eGFR levels. 1, 2, 3
Dosing Algorithm Based on Renal Function
eGFR ≥ 60 mL/min/1.73 m²
- Initial dose: 500 mg or 850 mg once daily (immediate-release) or 500 mg daily (extended-release)
- Titration: Increase by 500 mg/day or 850 mg/day every 7 days until maximum dose
- Maximum dose: Up to 2550 mg/day (immediate-release) or 2000 mg/day (extended-release)
- Monitoring: Check kidney function at least annually
eGFR 45-59 mL/min/1.73 m²
- Initial dose: 500 mg once daily
- Titration: Slower titration recommended
- Maximum dose: Standard dose may be continued, but consider dose reduction in certain conditions
- Monitoring: Check kidney function every 3-6 months
eGFR 30-44 mL/min/1.73 m²
- Initial dose: 500 mg once daily
- Maximum dose: Halve the maximum dose (approximately 1000-1250 mg/day)
- Monitoring: Check kidney function every 3-6 months
eGFR < 30 mL/min/1.73 m²
Important Considerations
Dose Titration
- Titrate doses slowly to minimize gastrointestinal side effects
- For immediate-release: Increase by 500 mg/day or 850 mg/day every 7 days
- For extended-release: Increase by 500 mg/day every 7 days 1, 2
Monitoring Requirements
- Monitor eGFR more frequently in patients with impaired renal function
- For eGFR 30-59 mL/min/1.73 m²: Check kidney function every 3-6 months
- For eGFR ≥ 60 mL/min/1.73 m²: Check kidney function annually
- Monitor vitamin B12 levels in patients on long-term metformin therapy (>4 years) 1, 2
Temporary Discontinuation
Metformin should be temporarily discontinued during:
- Acute illness with risk of dehydration
- Before iodinated contrast imaging procedures
- During bowel preparation for colonoscopy
- During major surgery 2, 3
Clinical Pearls and Pitfalls
Common Pitfalls
- Using creatinine alone for dosing decisions: eGFR is more accurate than serum creatinine for assessing renal function and determining metformin eligibility 4
- Failing to adjust dose with declining renal function: Regular monitoring of kidney function is essential to identify changes requiring dose adjustment 1, 2
- Not considering extended-release formulations: Extended-release metformin may have fewer gastrointestinal side effects compared to immediate-release formulations 5
Benefits of Appropriate Dosing
- Reduced risk of lactic acidosis while maintaining glycemic benefits
- Potential cardiovascular benefits even in patients with moderate renal impairment 2, 6
- Better gastrointestinal tolerability with extended-release formulations 5
Remember that metformin pharmacokinetics are significantly altered in renal impairment, with reduced clearance proportional to the decrease in renal function 7, 8. Appropriate dose adjustment is essential to maintain safety while preserving the benefits of this first-line therapy for type 2 diabetes.