Metformin Extended-Release Dose Conversion
For a patient currently taking 2000 mg per day of immediate-release metformin, the equivalent dose of extended-release (ER) metformin is 2000 mg once daily, taken with the evening meal. 1, 2
Direct Dose Equivalence
- Extended-release and immediate-release metformin formulations provide equivalent total daily dosing on a milligram-per-milligram basis. 1, 2
- The bioavailability (measured by area under the plasma concentration-time curve) of metformin ER is similar to the immediate-release formulation at comparable total daily doses, though the time to peak plasma concentration is prolonged (7 hours versus 3 hours). 3
- Clinical trials demonstrate that metformin ER 2000 mg once daily provides clinically similar efficacy to metformin IR 2000 mg given in divided doses, measured by changes in HbA1c and fasting plasma glucose. 2
Practical Conversion Strategy
- Switch directly from 2000 mg/day immediate-release to 2000 mg once daily extended-release, administered with the evening meal. 1, 2
- No dose titration is required when converting between formulations at equivalent total daily doses in patients already tolerating immediate-release metformin. 4, 2
- The maximum recommended dose for metformin ER is 2000 mg daily for most patients, though FDA labeling allows up to 2550 mg daily in divided doses. 1
Key Advantages of Extended-Release Formulation
- Once-daily dosing with the evening meal improves adherence compared to twice or three-times daily immediate-release dosing. 1, 4
- Patients switched from immediate-release to extended-release formulations—even those switched due to gastrointestinal intolerance—often better tolerate the ER formulation, with 77% of patients reporting freedom from GI side effects. 4, 5
- In one study, patients achieved the same clinical and metabolic benefits with a reduced average dose of metformin ER (1500 mg) compared to their previous standard metformin dose (1861 mg), with 83% preferring the ER formulation. 5
Important Renal Function Considerations
- Before converting, verify the patient's eGFR, as dose adjustments are mandatory for reduced renal function. 6, 1
- For eGFR 30-44 mL/min/1.73 m², reduce the total daily dose to 1000 mg (half the standard dose). 6, 1
- Metformin is contraindicated when eGFR falls below 30 mL/min/1.73 m². 6, 1
- Monitor eGFR at least annually in patients with normal renal function, and every 3-6 months when eGFR is <60 mL/min/1.73 m². 1
Common Pitfalls to Avoid
- Do not reduce the total daily dose when converting from immediate-release to extended-release formulations unless renal function is impaired. 2, 3
- Patients may report seeing "ghost tablets" in their stool (54% in one study)—this is the empty tablet shell and does not indicate malabsorption or treatment failure. 5
- Extended-release metformin bioavailability increases when taken with food (unlike immediate-release, which slightly decreases), so emphasize taking with the evening meal. 2, 3
- Monitor vitamin B12 levels in patients treated with metformin for more than 4 years, especially those with anemia or peripheral neuropathy. 1, 7