Maximum Daily Dose of Metformin
For adults with normal renal function (eGFR ≥60 mL/min/1.73 m²), the maximum daily dose of metformin is 2000–2550 mg, regardless of whether immediate-release or extended-release formulation is used. 1, 2
Dosing by Formulation
Immediate-Release Metformin
- Start with 500 mg or 850 mg once daily 1
- Titrate upward by 500 mg or 850 mg every 7 days 1, 2
- Maximum daily dose: 2000–2550 mg divided into 2–3 doses per day 1, 2
- Requires twice- or thrice-daily dosing due to shorter half-life (6.2 hours) 1
Extended-Release Metformin
- Start with 500 mg once daily 1
- Titrate upward by 500 mg weekly 1
- Maximum daily dose: 2000–2550 mg 1, 2
- Can be dosed once daily, typically with the evening meal 1
Dose Adjustments Based on Renal Function
The maximum dose must be reduced as kidney function declines to prevent drug accumulation and lactic acidosis risk. 3
| eGFR (mL/min/1.73 m²) | Maximum Daily Dose | Monitoring Frequency |
|---|---|---|
| ≥60 | 2000–2550 mg | Annually [3,1] |
| 45–59 | 2000 mg (consider reduction in elderly or those with liver disease/heart failure) [3,1] | Every 3–6 months [3,1] |
| 30–44 | 1000 mg (50% reduction required) [3,1,4] | Every 3–6 months [3,1] |
| <30 | Discontinue immediately (absolute contraindication) [3,1] | — |
Evidence Supporting Maximum Dosing
- Pharmacokinetic modeling demonstrates that doses up to 2250 mg daily in patients with normal kidney function maintain plasma concentrations below the safety threshold of 5 mg/L associated with lactic acidosis risk 4
- Population pharmacokinetic studies confirm that maximum doses of 2000–3000 mg daily are safe when eGFR ≥60 mL/min/1.73 m², with concentrations remaining below the 5 mg/L upper limit 5
Critical Safety Considerations
Temporary discontinuation is mandatory during acute illness, regardless of baseline renal function. 3, 1
- Hold metformin during sepsis, severe dehydration, vomiting, acute heart failure, or any condition causing volume depletion 3, 1
- Stop before iodinated contrast procedures in patients with eGFR 30–60 mL/min/1.73 m² who have liver disease, alcoholism, heart failure, or receive intra-arterial contrast; re-check eGFR 48 hours post-procedure before restarting 3
Monitoring Requirements
- Check eGFR at least annually when ≥60 mL/min/1.73 m² 3, 1
- Increase monitoring to every 3–6 months once eGFR drops below 60 mL/min/1.73 m² 3, 1
- Screen vitamin B12 levels after >4 years of therapy; approximately 7% develop deficiency 3, 1, 6
Common Prescribing Pitfalls
- Do not rely on serum creatinine alone—always calculate eGFR, especially in elderly or small-statured patients 3
- Do not continue annual monitoring once eGFR falls below 60 mL/min/1.73 m²; increase frequency to every 3–6 months 3
- Titrate dose gradually to minimize gastrointestinal side effects; consider switching to extended-release formulation if intolerance occurs 6