From the Guidelines
The starting dose of metformin for type 2 diabetes is typically 500 mg once or twice daily with food, as recommended by the American Diabetes Association standards of medical care in diabetes 1. This low initial dose helps minimize gastrointestinal side effects such as nausea, diarrhea, and abdominal discomfort, which are common when beginning metformin therapy. After 1-2 weeks of treatment, if the patient tolerates the medication well, the dose can be increased to 500 mg twice daily. Further gradual increases can be made, usually in increments of 500 mg every 1-2 weeks, until the target dose is reached. The typical effective dose ranges from 1,000 to 2,000 mg daily, divided into two doses (with morning and evening meals), with a maximum recommended daily dose of 2,550 mg. Extended-release formulations are also available, which can be taken once daily and may cause fewer gastrointestinal side effects. Metformin works by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity, which helps lower blood glucose levels without causing hypoglycemia when used alone 2, 3, 4. It is essential to monitor patients for potential side effects, including gastrointestinal issues and vitamin B12 deficiency, especially those with anemia or peripheral neuropathy 1. A patient-centered approach should be used to guide the choice of pharmacologic agents, considering factors such as efficacy, hypoglycemia risk, effect on weight, side effects, cost, and patient preferences 1, 2.
From the FDA Drug Label
The recommended starting dose of metformin hydrochloride tablets are 500 mg orally twice a day or 850 mg once a day, given with meals. The starting dose of metformin for type 2 diabetes is 500 mg orally twice a day or 850 mg once a day, given with meals 5.
- The dose can be increased in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability.
- The maximum dose is 2550 mg per day, given in divided doses.
From the Research
Starting Dose of Metformin for Type 2 Diabetes
- The starting dose of metformin for type 2 diabetes is not explicitly stated in the provided studies 6, 7, 8, 9, 10.
- However, study 8 mentions that metformin XR (extended-release) was evaluated at dosages of 500 mg, 1000 mg, 1500 mg, and 2000 mg once daily, suggesting that these dosages may be considered for type 2 diabetes treatment.
- The American Diabetes Association's (ADA) guidelines, mentioned in study 6, recommend metformin as the first-line treatment for patients with type 2 diabetes, but do not specify a starting dose.
- Study 8 also reports that metformin XR 1000 mg once daily was commonly used in the evaluation, and that a clear dose-response relationship was evident at doses up to 1500 mg.
Dose-Response Relationship
- Study 8 found a clear dose-response relationship for metformin XR 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) in HbA(1C) levels.
- The study suggests that metformin XR 2000 mg once daily and 1000 mg twice daily had similar efficacy, with mean treatment differences vs. placebo in HbA(1C) of -1.0% and -1.2%, respectively.
Safety and Efficacy
- Study 8 reports that metformin XR was well-tolerated, with gastrointestinal side effects being more common with metformin XR vs. placebo, but few patients withdrew due to these side effects.
- Study 7 found that sulfonylureas as add-on therapy to metformin were associated with increased risk of all-cause mortality and major hypoglycemic episodes compared with other oral hypoglycemic agents.