Maximum Metformin Dose in Adults with Normal Renal Function
For adults with normal renal function (eGFR ≥60 mL/min/1.73 m²), the maximum daily dose of metformin is 2000–2550 mg for both immediate-release and extended-release formulations. 1
Dosing by Formulation
Immediate-Release Metformin
- Initial dose: 500 mg or 850 mg once daily 2
- Titration: Increase by 500 mg/day or 850 mg/day every 7 days 2
- Maximum daily dose: 2000–2550 mg 1
- Dosing frequency: Requires 2–3 times daily administration due to the 6.2-hour half-life 1
Extended-Release Metformin
- Initial dose: 500 mg once daily 2
- Titration: Increase by 500 mg/day every 7 days 2
- Maximum daily dose: 2000–2550 mg 1
- Dosing frequency: Once-daily dosing, typically with the evening meal or at bedtime 1
- Pharmacokinetics: Time to maximum concentration is approximately 7 hours at steady state, compared to 3 hours for immediate-release 3
Evidence Supporting Maximum Dose
The 2000–2550 mg maximum is derived from multiple high-quality sources. The KDIGO 2022 guidelines reference titration to "maximum dose" without exceeding safety thresholds 2, while pharmacokinetic modeling demonstrates that 2250 mg daily in patients with normal kidney function maintains steady-state concentrations below the 5 mg/L safety threshold associated with lactic acidosis risk 4. The extended-release formulation achieves equivalent area under the curve (AUC) to immediate-release at comparable total daily doses, with a 36% higher peak concentration when 2000 mg XR once daily is compared to 1000 mg IR twice daily 3.
Monitoring Requirements
- Renal function: Check eGFR at least annually when eGFR ≥60 mL/min/1.73 m² 2, 1
- Vitamin B12: Monitor in patients on metformin for more than 4 years, as approximately 7% develop deficiency 2, 1
Critical Safety Considerations
Temporary discontinuation is mandatory during acute illness that may impair renal function (sepsis, severe dehydration, vomiting, hospitalization with acute kidney injury risk) regardless of baseline eGFR, as these conditions reduce metformin clearance and increase lactic acidosis risk 1. Metformin should also be held before iodinated contrast procedures in patients with liver disease, alcoholism, or heart failure, with eGFR rechecked 48 hours post-procedure before restarting 1.
The mean accumulation ratio of extended-release metformin is 1.0, indicating no drug accumulation with multiple-dose administration at approved doses 3. Both formulations are eliminated unchanged in urine, making renal function the primary determinant of clearance 1, 5.