Effects of dosage and dosing frequency on the efficacy and safety of high‐dose metformin in Japanese patients with type 2 diabetes mellitus

AIMS/INTRODUCTION: Differences in the efficacy and safety of antidiabetic drugs among different ethnic groups are well documented. Metformin is widely used in the treatment of type 2 diabetes in Western countries, but high doses of metformin have been approved only recently for clinical use in Japan. The aim of the present study was to investigate the effects of dosage and dosing frequency on the efficacy and safety of high‐dose metformin in Japanese patients. MATERIALS AND METHODS: A total of 71 Japanese patients with type 2 diabetes were prospectively studied for the effects of dosage and dosing frequency on the efficacy and safety of metformin during hospitalization. Dose effects were studied in 27 patients treated with 0, 500, 1,000, 1,500 and 2,250 mg/day of metformin. The effect of dosing frequency was compared in 56 patients with 1,500 mg/day of metformin administered either two or three times per day. RESULTS: Significant dose‐dependent improvement in daily profiles of blood glucose was observed with metformin dosages up to 1,500 mg/day, with a trend towards further improvement observed at 2,250 mg/day. The efficacy of 1,500 mg of metformin was comparable when the drug was administered either two or three times per day. The most frequently reported side‐effects were gastrointestinal symptoms, which were not affected by the dosage or dosing frequency of metformin. CONCLUSIONS: These results show that the efficacy of high‐dose metformin is dose‐dependent in Japanese patients. The efficacy and safety of metformin were similar when the drug was administered either two or three times per day.