Maximum Approved Daily Dose of Metformin
For adults with normal renal function (eGFR ≥60 mL/min/1.73 m²), the maximum approved daily dose of metformin is 2550 mg, given in divided doses. 1
FDA-Approved Dosing
The FDA label establishes the following maximum dosing parameters for metformin immediate-release formulation 1:
- Maximum total daily dose: 2550 mg for adults with eGFR ≥60 mL/min/1.73 m² 1
- Practical maximum: 2000 mg daily is the most commonly used ceiling, as doses above 2000 mg may be better tolerated when divided three times daily with meals 1
- Standard titration: Start at 500 mg twice daily or 850 mg once daily, then increase by 500 mg weekly or 850 mg every 2 weeks based on glycemic response 1
Guideline-Based Dosing Recommendations
Major diabetes and nephrology guidelines align closely with FDA labeling 2, 3:
- Target dose for most patients: 2000 mg daily (typically 1000 mg twice daily), which provides optimal efficacy with better tolerability than the absolute maximum 2
- Extended-release formulation maximum: 2000 mg once daily with the evening meal 2, 3
- The 2022 KDIGO and ADA consensus statements recommend maximum doses of 2000–2550 mg daily for patients with preserved renal function 3
Renal Function Thresholds
Dosing must be adjusted based on eGFR 1, 2, 3:
| eGFR (mL/min/1.73 m²) | Maximum Daily Dose | Monitoring Frequency |
|---|---|---|
| ≥60 | 2000–2550 mg | Annually |
| 45–59 | 2000 mg (consider reduction in high-risk patients) | Every 3–6 months |
| 30–44 | 1000 mg (50% reduction required) | Every 3–6 months |
| <30 | Contraindicated—discontinue immediately | — |
Pediatric Dosing
For children aged 10 years and older 2, 1:
- Maximum dose: 2000 mg daily in divided doses (typically 1000 mg twice daily) 2, 1
- Start at 500 mg twice daily and titrate by 500 mg weekly 1
Critical Safety Considerations
Temporary discontinuation is mandatory during 2, 3, 4:
- Acute illness causing volume depletion (sepsis, severe diarrhea, vomiting, dehydration) 2, 3
- Hospitalization with elevated acute kidney injury risk 2, 3
- Iodinated contrast procedures in patients with eGFR 30–60 mL/min/1.73 m², history of liver disease, alcoholism, heart failure, or intra-arterial contrast administration 3, 1
- Re-evaluate eGFR 48 hours post-contrast before restarting 3, 1
Long-term monitoring requirements 2, 3:
- Check vitamin B12 levels in patients on metformin >4 years, as approximately 7% develop deficiency 2, 3
- Monitor eGFR at least annually when ≥60 mL/min/1.73 m², and every 3–6 months when <60 mL/min/1.73 m² 2, 3
Common Pitfalls
- Do not exceed 2550 mg daily even in patients with poor glycemic control—add a second agent instead 2
- Do not use serum creatinine alone to guide dosing; always calculate eGFR, especially in elderly or low-body-weight patients 4
- Do not continue doses >1000 mg daily when eGFR falls to 30–44 mL/min/1.73 m²—this substantially increases lactic acidosis risk 2, 3, 1