Maximum Daily Dose of Glucophage XR
The maximum recommended daily dose of extended-release metformin (Glucophage XR) is 2000 mg once daily, taken with the evening meal. 1, 2, 3
Standard Dosing Parameters
The FDA-approved maximum dose is 2000 mg once daily for the extended-release formulation, which provides equivalent glycemic control to immediate-release metformin 1000 mg twice daily at comparable total daily doses. 2, 3
The extended-release formulation is specifically engineered for once-daily administration and should not be split into multiple daily doses—if twice-daily dosing is needed for tolerability, switch to immediate-release metformin instead. 1
Peak plasma concentrations with metformin XR 2000 mg once daily reach approximately 1.8 mcg/mL, with absorption occurring over 4-8 hours (median 7 hours). 4, 2
Dose Titration to Maximum
Start at 500 mg once daily with the evening meal and increase by 500 mg increments every 7 days based on glycemic response and gastrointestinal tolerability until reaching the target dose of 2000 mg daily. 1, 5
The dose-response relationship is clear up to 1500 mg daily, with 2000 mg providing similar efficacy to 1500 mg but offering an option for patients requiring maximal metformin dosing before adding second agents. 3
Most patients achieve optimal therapeutic benefit at 2000 mg daily, which reduces HbA1c by approximately 1.0-1.5% from baseline. 3
Critical Renal Function Limitations
The maximum dose must be adjusted based on kidney function:
| eGFR (mL/min/1.73 m²) | Maximum Daily Dose | Monitoring Frequency |
|---|---|---|
| ≥60 | 2000 mg once daily | Annually |
| 45-59 | 2000 mg once daily (consider reduction in high-risk patients) | Every 3-6 months |
| 30-44 | 1000 mg once daily (half standard dose) | Every 3-6 months |
| <30 | Contraindicated—discontinue | N/A |
Common Pitfalls and How to Avoid Them
Never exceed 2000 mg daily of metformin XR—if glycemic targets are not met after 3 months at maximum dose, add a second agent (SGLT-2 inhibitor or GLP-1 receptor agonist) rather than increasing metformin further. 1, 5
Do not confuse the maximum dose of extended-release (2000 mg once daily) with immediate-release metformin, which can be dosed up to 2550 mg daily in divided doses (typically 1000 mg twice daily plus 500 mg with dinner). 1, 5
Temporarily discontinue metformin XR before procedures with iodinated contrast, during hospitalizations, or when acute illness may compromise renal or hepatic function to prevent lactic acidosis. 1, 5
Monitor for vitamin B12 deficiency in patients on metformin for more than 4 years, especially those with peripheral neuropathy or anemia, as long-term use can impair B12 absorption. 1, 5
Tolerability Advantages at Maximum Dose
Extended-release metformin 2000 mg once daily is better tolerated than immediate-release metformin at equivalent total daily doses, with fewer gastrointestinal side effects (11.9% vs 26.3% when switched from IR to XR). 7, 8
The once-daily dosing improves adherence compared to twice- or three-times-daily immediate-release formulations, which may translate to better long-term glycemic control. 9, 8
If gastrointestinal side effects occur during titration to 2000 mg, decrease to the previous lower dose (1500 mg) and attempt advancement after 1-2 weeks rather than abandoning metformin therapy. 1