Quantifying the Effect of Metformin 1000 mg/day in Japanese Patients with Type 2 Diabetes


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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Suzuki, K. , Yoshioka, T. and Wakui, Y. (2014) Quantifying the Effect of Metformin 1000 mg/day in Japanese Patients with Type 2 Diabetes. International Journal of Clinical Medicine, 5, 894-901. doi: 10.4236/ijcm.2014.515120.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Defronzo, R.A. and Goodman, A.M. (1995) Efficacy of Metformin in Patients with Non-Insulin-Dependent Diabetes Mellitus. The Multicenter Metformin Study Group. The New England Journal of Medicine, 333, 541-549.
[2] UK prospective Diabetes Study (UKPDS) Group (1998) Effect of Intensive Blood-Glucose Control with Metformin on Complications in Overweight Patients with Type 2 Diabetes (UKPDS 34). Lancet, 352, 854-865.
[3] Holman, R.R., Paul, S.K., Bethel, M.A., et al. (2008) 10-Years Follow-Up of Intensive Glucose Control in Type 2 Diabetes. The New England Journal of Medicine, 359, 1577-1589.
[4] International Diabetes Federation (2005) Glucose Control: Oral Therapy. Global Guideline for Type 2 Diabetes. 35-38,
[5] Nathan, D.M., Buse, J.B., Davidson, M.B., et al. (2008) Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: Update Regarding Thiazolidinediones: A Consensus Statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 31, 173-175.
[6] Garber, A.J., Duncan, T.G., Goodman, A.M., Mills, D.J. and Rohlf, J.L. (1997) Efficacy of Metformin in type II Diabetes: Results of a Bouble-Blind, Placebo-Controlled, Dose-Response Trial. The American Journal of Medicine, 103, 491-497.
[7] Kaku, K., Tajima, N. and Kawamori, Y. (2006) Melbin Observational Research (MORE) Study of Metformin Therapy in Patients with Type 2 Diabetes Mellitus. Tonyobyo (Diabetes), 49, 325-331. In Japanese.
[8] Sumintani, S., Morita, S., Utsu, Y., Mukai, K., Miki, S., Sato, B., Nakamura, H. and Kasayama, S. (2012) Effectiveness of Metformin and Lifestyle Interventions as an Initial Treatment in Japanese Patients with Observational Study. The Journal of Medical Investigation, 59, 166-173.
[9] Edited by the Japan Diabetes Society (2014-2015) Treatment Guide for Diabetes. 24-25.
[10] Okuno, Y., Sakaguchi, K., Komada, H., Hashimoto, N., Hirota, Y., Nakamura, T., Ogawa, W. and Seino, S. (2013) Correlation of Serum CPR to Plasma Glucose Ratio with Various Indices of Insulin Secretion and Diseases Duration in Type 2 Diabetes. Kobe Journal of Medical Sciences, 59, E44-E53.
[11] Baily, C.J., et al. (1994) Insulin Requirement for the Antihyperglycaemic Effect of Metformin. British Journal of Pharmacology, 111, 793-796.
[12] Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M.F., Goodyear, L.J. and Moller, D.E. (2001) Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action. Journal of Clinical Investigation, 108, 1167-1174.
[13] Miller, R.A., Chu, Q., Xie, J., Foretz, M., Viollet, B. and Birnbaum, M.J. (2013) Biguanides Suppress Hepatic Glucagon Signalling by Decreasing Production of Cyclic AMP. Nature, 494, 256-260.
[14] Bailey, C.J. and Howlett, H.C.S. (2008) Tolerability of Metformin. In: Bailey, C.J., Campbell, I.W., Chan, J.C.N., et al, Metformin: The Gold Standard, John Wiley and Sons Ltd., Chichester, 173-178.

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