Maximum Dosage of Metformin
The maximum approved daily dose of metformin is 2550 mg per day for immediate-release formulations, given in divided doses, and 2000 mg per day for extended-release formulations. 1, 2
Immediate-Release Metformin Dosing
- The recommended starting dose is 500 mg orally twice a day or 850 mg once a day, given with meals 2
- Dose should be increased in increments of 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability 2
- Maximum dose of 2550 mg per day should be given in divided doses 2
- Doses above 2000 mg may be better tolerated when given three times a day with meals 2
Extended-Release Metformin Dosing
- Initial dose is 500 mg daily 1
- Titrate upwards by 500 mg daily every 7 days until maximum dose 1
- Maximum dose is 2000 mg daily 1
- Extended-release formulation allows for once-daily dosing 3
- May have better gastrointestinal tolerability compared to immediate-release formulation 4, 3
Dosing Adjustments Based on Renal Function
- For patients with eGFR ≥60 mL/min/1.73 m²: Continue same dose 1
- For patients with eGFR 45-59 mL/min/1.73 m²: Consider dose reduction in certain conditions 1
- For patients with eGFR 30-44 mL/min/1.73 m²: Halve the dose (maximum 1000 mg daily) 1
- For patients with eGFR <30 mL/min/1.73 m²: Metformin is contraindicated 1, 2
Pediatric Dosing
- For patients 10 years and older: Starting dose is 500 mg twice daily 2
- Increase in increments of 500 mg weekly based on glycemic control and tolerability 2
- Maximum pediatric dose is 2000 mg per day, given in divided doses twice daily 2
Important Monitoring Considerations
- Monitor eGFR at least annually in all patients, and every 3-6 months in patients with eGFR <60 mL/min/1.73 m² 1
- Monitor vitamin B12 levels in patients treated with metformin for more than 4 years 1
- To minimize gastrointestinal side effects, start with a low dose and titrate slowly 4, 3
Clinical Pearls
- Extended-release metformin reaches maximum plasma concentrations more slowly than immediate-release formulations (7 hours vs. 3 hours) 5
- Extended-release formulation may improve patient adherence due to once-daily dosing and potentially fewer gastrointestinal side effects 3, 6
- Patients switched from immediate-release to extended-release formulations often experience fewer gastrointestinal side effects at comparable doses 4, 6
- "Ghost tablets" (empty shells of the medication) may appear in the stool with extended-release formulations but do not affect efficacy 6