From the Guidelines
The maximum recommended dose of metformin 1000 mg XR for Type 2 Diabetes Mellitus (T2DM) is 2000 mg once daily. This is based on the most recent and highest quality study available, which suggests that metformin is effective and safe, and reduces risks of microvascular complications, cardiovascular events, and death 1. Patients should start with a lower dose, typically 500 mg or 1000 mg once daily, and gradually increase to the maximum dose as needed and tolerated to achieve glycemic control.
Key Considerations
- Dose adjustments should be made every 1-2 weeks based on blood glucose readings and side effect profile.
- Metformin works by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity.
- Renal function should be assessed before starting therapy and periodically thereafter, as dose reduction is necessary for patients with reduced kidney function (eGFR <45 mL/min/1.73m²), and metformin is contraindicated in severe renal impairment (eGFR <30 mL/min/1.73m²) 1.
- Common side effects include diarrhea, nausea, and abdominal discomfort, which often improve with time.
Important Notes
- The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration and/or using extended-release formulation 1.
- Metformin use is also associated with increased risk of vitamin B12 deficiency and worsening of symptoms of neuropathy, suggesting periodic testing of vitamin B12 levels 1.
From the FDA Drug Label
2 DOSAGE AND ADMINISTRATION
- 1 Adult Dosage Metformin Hydrochloride Tablets The recommended starting dose of metformin hydrochloride tablets are 500 mg orally twice a day or 850 mg once a day, given with meals. Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2550 mg per day, given in divided doses.
The recommended maximum dose of metformin for Type II Diabetes Mellitus (TIIDM) is 2550 mg per day, given in divided doses 2.
From the Research
Recommended Max Dose of Metformin 1000 mg XR for TIIDM
- The maximum recommended dose of metformin 1000 mg XR for type 2 diabetes mellitus (TIIDM) is not explicitly stated in the provided studies as 1000 mg XR, but rather as a total daily dose of metformin.
- According to the study 3, the dose-response relationship of metformin XR was evaluated, and a clear dose-response relationship was evident at doses up to 1500 mg, with treatment differences vs. placebo of -0.6% (500 mg once daily), -0.7% (1000 mg once daily), -1.0% (1500 mg once daily) and -1.0% (2000 mg once daily).
- The study 4 mentions that patients were titrated to a maximum dose of 2000 mg/day of metformin XR, and the study 5 evaluated the efficacy and safety of a novel extended-release metformin in patients with type 2 diabetes, with treatment regimens including 1,500 mg/day q.d., 1,500 mg/day twice daily, or 2,000 mg/day q.d.
- The study 6 does not provide information on the maximum recommended dose of metformin 1000 mg XR, but rather compares the efficacy and tolerability of once- or twice-daily extended release metformin with thrice-daily immediate release metformin in patients with type 2 diabetes mellitus.
Key Findings
- Metformin XR was well tolerated, with gastrointestinal side effects being more common with metformin XR vs. placebo, but few patients withdrew for this reason 3.
- Once-daily metformin XR presents an effective and well-tolerated therapeutic option for delivering metformin in a convenient manner, which supports good compliance with therapy 3.
- The efficacy of metformin XR 2000 mg once daily and 1000 mg twice daily were similar, with mean treatment differences vs. placebo in HbA(1C) being -1.0% and -1.2%, respectively 3.