Objective: To examine the effect of high-dose metformin on glucose metabolism in Japanese patients with type 2 diabetes. Method: A total of 144 patients with type 2 diabetes who could be followed up for 6 months after their dose of metformin was increased to 1000 mg/day (from 750 mg/day or less) were examined. The dose of metformin was increased from 750 mg/day in 70 subjects (250-mg dose increase) and from 500 mg/day in 74 subjects (500-mg dose increase). Results: After the dose increased to 1000 mg/day, HbA1c was significantly decreased by 0.65% ± 0.7%, 0.42% ± 0.5%, and 0.87% ± 0.7% in all subjects, the 250-mg dose increase group, and the 500-mg dose increase group, respectively. No significant change was observed in weight. Analysis by BMI (<25 kg/m2 and ≥25 kg/m2) revealed a comparable significant decrease in HbA1c in all subjects, the 250-mg dose increase group, and the 500-mg dose increase group. Analysis by duration of diabetes showed a significant decrease in HbA1c regardless of the duration. Conclusion: Increasing the metformin dose to 1000 mg/day showed a significant antihyperglycemic effect over 6 months in Japanese patients with type 2 diabetes. Blood glucose improved regardless of the duration of diabetes or the presence or absence of obesity. Overall tolerability was favorable.
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