Maximum Metformin Dosage
For adults with type 2 diabetes and normal kidney function (eGFR ≥60 mL/min/1.73 m²), the maximum recommended dose of metformin is 2550 mg per day for immediate-release formulations and 2000 mg per day for extended-release formulations. 1
Immediate-Release Metformin Dosing
- Maximum daily dose: 2550 mg, divided into multiple doses taken with meals 1
- Start at 500 mg twice daily or 850 mg once daily, with meals 1
- Titrate upward by 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability 1
- Doses above 2000 mg are better tolerated when given three times daily with meals rather than twice daily 1
Extended-Release Metformin Dosing
- Maximum daily dose: 2000 mg once daily 2
- Start at 500 mg once daily 3, 2
- Titrate upward by 500 mg every 7 days until maximum dose is reached 3, 2
- Extended-release formulations offer improved gastrointestinal tolerability and once-daily dosing convenience 4, 5
Dose Adjustments Based on Kidney Function
Critical kidney function thresholds require mandatory dose modifications:
eGFR ≥60 mL/min/1.73 m²
- No dose adjustment needed 3, 6, 2
- Full maximum doses can be used 1
- Monitor kidney function at least annually 3
eGFR 45-59 mL/min/1.73 m²
- Continue current dose without further increases 3, 6
- Consider dose reduction in elderly patients or those with liver disease 3, 6
- Increase monitoring frequency to every 3-6 months 3, 6
eGFR 30-44 mL/min/1.73 m²
- Reduce dose to half the maximum recommended dose (maximum 1000 mg daily for immediate-release, 500 mg twice daily) 3, 6
- Do not initiate metformin in this range 1
- Monitor kidney function every 3-6 months 3, 6
eGFR <30 mL/min/1.73 m²
- Metformin is absolutely contraindicated 3, 6, 1
- Stop metformin immediately if eGFR falls below this threshold 3, 1
- Do not initiate metformin 3, 1
Important Clinical Considerations
Temporary discontinuation is required in specific situations:
- Discontinue before or at the time of iodinated contrast imaging procedures in patients with eGFR 30-60 mL/min/1.73 m², history of liver disease, alcoholism, heart failure, or when intra-arterial contrast will be administered 1
- Re-evaluate eGFR 48 hours after imaging; restart only if renal function is stable 1
- Implement "sick day rules" to stop metformin during serious intercurrent illness that increases acute kidney injury risk 6
Long-term monitoring requirements:
- Monitor vitamin B12 levels in patients on metformin for more than 4 years due to risk of deficiency 3, 6, 2, 7
- The mean plasma concentration should be maintained below 2.5 mg/L to minimize lactic acidosis risk 8
Common Pitfalls to Avoid
- Never exceed 2550 mg daily for immediate-release or 2000 mg daily for extended-release formulations, even in patients with excellent kidney function 1
- Do not continue metformin when eGFR drops below 30 mL/min/1.73 m², as this dramatically increases lactic acidosis risk 3, 1
- Gastrointestinal side effects occur in less than 20% of patients and typically resolve with dose reduction or switching to extended-release formulations 9, 4, 5
- Patients switched from immediate-release to extended-release metformin experience significantly fewer GI adverse events (26.34% vs 11.71%) 5