Metformin Dosage Recommendations
The recommended starting dose of metformin is 500 mg orally twice daily or 850 mg once daily with meals, with gradual titration by 500 mg weekly or 850 mg every 2 weeks up to a maximum of 2550 mg daily in divided doses, based on glycemic control and tolerability. 1
Initial Dosing and Titration
Immediate Release (IR) Formulation:
- Start with 500 mg once or twice daily, or 850 mg once daily with meals
- Titrate upward by 500 mg/day or 850 mg/day every 7 days if no gastrointestinal side effects occur
- Maximum effective dose: up to 2550 mg daily (doses above 2000 mg may be better tolerated when given three times daily with meals)
- Common maintenance dose: 850 mg twice daily 2, 1
Extended Release (XR) Formulation:
- Start with 500 mg once daily with the evening meal
- Titrate upward by 500 mg/day every 7 days based on tolerance
- Maximum dose: 2000 mg daily 3, 4
- May offer better gastrointestinal tolerability compared to IR formulation 5
Dose Adjustments Based on Renal Function
Renal function must be assessed before initiating metformin and periodically thereafter:
| eGFR (mL/min/1.73 m²) | Recommendation |
|---|---|
| ≥60 | Continue standard dosing; monitor annually |
| 45-59 | Consider dose reduction; monitor every 3-6 months |
| 30-44 | Reduce dose by 50% (halve the maximum dose); monitor every 3-6 months |
| <30 | Contraindicated - do not use metformin [2,1] |
Special Considerations
Gastrointestinal Side Effects Management:
- If gastrointestinal side effects occur during dose titration, decrease to the previous lower dose and attempt to advance more slowly 2
- Extended-release formulation may help reduce gastrointestinal side effects while maintaining efficacy 5, 4
Temporary Discontinuation:
Temporarily discontinue metformin:
- During acute illness with risk of dehydration
- Before iodinated contrast imaging procedures (especially in patients with eGFR 30-60 mL/min/1.73 m²)
- Before major surgery
- During any condition that may cause acute kidney injury 3, 1
Long-term Monitoring:
- Monitor vitamin B12 levels in patients on metformin for more than 4 years 2, 3
- Assess glycemic control with HbA1c every 3 months until target is achieved
Pediatric Dosing
- For patients 10 years and older: Start with 500 mg twice daily with meals
- Increase by 500 mg weekly based on glycemic control and tolerability
- Maximum dose: 2000 mg daily in divided doses 1
Efficacy Considerations
- Dose-response relationship is evident up to 1500 mg daily, with diminishing additional benefit at higher doses 4
- Once-daily extended-release formulation at 2000 mg shows similar efficacy to 1000 mg twice daily of the same formulation 4
Metformin remains the first-line agent for type 2 diabetes management, with dosing that should be carefully titrated to balance glycemic efficacy with tolerability, particularly considering renal function and gastrointestinal side effects.