Metformin XR Dosing Schedule
Metformin Extended Release (XR) should be dosed once daily, typically with the evening meal. 1
Dosing Guidelines for Metformin XR
- Initial dosing of metformin XR should start at 500 mg once daily 2
- Dose can be titrated upward by 500 mg every 7 days until the maximum effective dose is reached 2
- The maximum effective dose is typically 2000 mg once daily 1, 3
- Once-daily dosing is appropriate and effective for metformin XR, unlike immediate-release metformin which requires twice-daily dosing 3, 4
Pharmacokinetic Rationale for Once-Daily Dosing
- Metformin XR has slower absorption than immediate-release metformin (time to maximum plasma concentration = 7 hours versus 3 hours for IR) 3
- At steady state, the area under the curve (AUC) for metformin XR once daily is comparable to the same total daily dose of immediate-release metformin given twice daily 1, 3
- The extended-release formulation maintains effective plasma levels over 24 hours, eliminating the need for multiple daily doses 3, 4
Clinical Benefits of Once-Daily Dosing
- Once-daily dosing of metformin XR has shown similar glycemic control to twice-daily dosing regimens 4
- Metformin XR 2000 mg once daily provides similar efficacy to metformin IR 1000 mg twice daily in reducing HbA1c (treatment differences vs. placebo of -1.0% and -1.2%, respectively) 4
- Once-daily dosing may improve medication adherence compared to multiple daily dosing regimens 5
- Gastrointestinal side effects may be reduced with the XR formulation compared to immediate-release metformin 6, 5
Renal Function Considerations
- For patients with eGFR ≥60 ml/min/1.73 m², no dose adjustment is needed 2
- For patients with eGFR 45-59 ml/min/1.73 m², consider dose reduction in certain conditions 2
- For patients with eGFR 30-44 ml/min/1.73 m², halve the dose 2
- Metformin XR should not be used in patients with eGFR <30 ml/min/1.73 m² 2
Monitoring Recommendations
- Monitor kidney function at least annually in patients with normal renal function and every 3-6 months in patients with eGFR <60 ml/min/1.73 m² 2
- Monitor for vitamin B12 deficiency in patients treated with metformin for more than 4 years 2
- Assess for gastrointestinal side effects, particularly during dose titration 6, 5
Common Pitfalls to Avoid
- Avoid twice-daily dosing of metformin XR as it provides no additional benefit over once-daily dosing and may reduce adherence 3, 4
- Do not crush or split metformin XR tablets as this would destroy the extended-release mechanism 1
- Temporary discontinuation may be necessary during procedures using iodinated contrast, during hospitalizations, or when acute illness may compromise renal or liver function 2
- Food decreases the extent and slightly delays the absorption of metformin; however, metformin XR is designed to be taken with a meal 1
By following these guidelines for once-daily dosing of metformin XR, clinicians can optimize glycemic control while potentially improving patient adherence and minimizing side effects.