Metformin monotherapy in children and adolescents with type 2 diabetes mellitus in Japan
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To evaluate the safety and effectiveness of metformin monotherapy for 52 weeks, including 24 weeks of treatment and a 28-week extension period for evaluation of long-term safety, in 37 Japanese pediatric patients with type 2 diabetes mellitus.
Research design and methods
This study design was an open-label, non-randomized, multicenter trial. The primary effectiveness endpoint was the changes from baseline to the final visit at 24 weeks in HbA1c. The secondary endpoints were the rate for achieving the treatment goal, and the changes in glycated albumin, fasting blood glucose, fasting insulin, HOMA-IR, and fasting serum lipids. Metformin was administrated at the dose of 500 mg/day up to a maximum of 2000 mg/day taken in two or three divided doses.
The mean change of HbA1c at the final visit at 24 weeks for 20 metformin-naïve patients (Group A) was − 0.66 ± 0.95% and that of 17 already-on metformin patients (Group B) was − 0.98 ± 1.62%. These figures proved the effectiveness of metformin as defined before the study. Secondary effectiveness endpoints were also improved. The improvement of blood glucose, fasting insulin and serum lipid levels proved the effectiveness of metformin without increasing body weight. Adverse effects such as nausea and diarrhea were observed in 35 of the 37 subjects and drug-related adverse events were observed in 19 patients. However, these events were not serious and did not increase with long-term treatment.
Metformin is safe and effective for Japanese pediatric patients with T2DM.
KeywordsMetformin Metformin monotherapy Childhood and adolescent T2DM Safety Adverse effects
Type 2 diabetes mellitus
Type 1 diabetes mellitus
Fasting plasma glucose
Homeostasis model assessment for insulin resistance
Full analysis set
Body mass index standard deviation score
International Society for Pediatric and Adolescent Diabetes
Good clinical practice
National Glycohemoglobin Standardization Program
Adverse drug reactions
The first clinical trial was supported by a Grant for clinical research from the Ministry of Health, Labor and Welfare of Japan. We also thank Eriko Aoyama, Miwa Nonaka, and Chie Takami of the Research Center for Clinical Pharmacology, Academic Clinical Trial Unit of Kitasato University, for analyzing the data from each investigator in the first clinical trial. We thank the study participants, the investigators and contributors from each study site of the first and second clinical trials.
Compliance and ethical standards
Conflicts of interest
This clinical trial was funded by Sumitomo Dainippon Pharma Co., Ltd. NM and SA are co-first authors and the chairpersons of the first and second trials, respectively, and contributed to the discussion and wrote the manuscript. SS and SA were members of the coordinating committee for the first trial and SA, SS and TU for the second trial. NM and NK are members of the safety evaluation committee for the second trial. All of these members have received honoraria from Sumitomo Dainippon Pharma. No other potential conflicts of interest relevant to this article were reported. HK and YY are employees of Sumitomo Dainippon Pharma and managed the second trial and carried out statistical analysis, respectively.
Human rights statement
All procedures followed were in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.
Informed consent or a substitute for it was obtained from all patients included in the study.
This study was approved by the ethics committee of the Sumitomo Dainippon Pharma (approval no. D3004001, approval date: 19 April 2011) and by the ethics committee of Saitama Medical University (approval no. 918, approval date: 24 May 2011).
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