Efficacy and Safety of Empagliflozin Monotherapy for 52 Weeks in Japanese Patients with Type 2 Diabetes: A Randomized, Double-Blind, Parallel-Group Study
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The aim of this randomized, double-blind, parallel-group study was to investigate the safety and efficacy of empagliflozin monotherapy for 52 weeks in Japanese patients with type 2 diabetes (T2DM).
In a 12-week dose-finding period, patients [N = 547; mean baseline glycosylated hemoglobin (HbA1c) 7.92–8.02%] received empagliflozin (5, 10, 25, or 50 mg) or placebo. In a 40-week extension period, patients on empagliflozin 10 or 25 mg continued the same treatment and patients on other doses were reallocated to empagliflozin 10 or 25 mg. Outcomes at week 52 included changes from baseline in HbA1c, fasting plasma glucose (FPG), weight and blood pressure (BP) in patients who received empagliflozin 10 or 25 mg in both the initial 12 weeks and the extension and safety in patients treated with ≥1 dose of empagliflozin 10 or 25 mg.
Adjusted mean ± SE changes in HbA1c from baseline at week 52 were –0.67 ± 0.09% and −0.86 ± 0.09%, in FPG were −24.7 ± 3.2 mg/dL and −31.3 ± 3.4 mg/dL, and in body weight were −3.1 ± 0.4 kg and −3.1 ± 0.4 kg, with empagliflozin 10 and 25 mg, respectively. Both doses reduced systolic and diastolic BP. Adverse events were reported in 70.8% and 66.8% of patients on empagliflozin 10 and 25 mg, respectively. Confirmed hypoglycemic adverse events (plasma glucose ≤70 mg/dL and/or requiring assistance) were reported in one patient per group.
Empagliflozin monotherapy for 52 weeks led to sustained reductions in HbA1c, FPG, weight and BP and was well tolerated in Japanese patients with T2DM.
Boehringer Ingelheim and Eli Lilly and Company.
KeywordsEmpagliflozin Japanese Monotherapy Sodium glucose cotransporter 2 (SGLT2 inhibitor) Type 2 diabetes
Sponsorship and article processing charges for this study were funded by Boehringer Ingelheim and Eli Lilly and Company. Medical writing assistance, funded by Boehringer Ingelheim, was provided by Clare Ryles and Elizabeth Ng of Fleishman-Hillard Group, Ltd. during the preparation of this manuscript. The authors were fully responsible for all content and editorial decisions at all stages of manuscript development and have approved the final version. These data have been presented in poster format at the 49th Annual Meeting of the European Association for the Study of Diabetes (EASD), 23–27 September 2013, Barcelona, Spain, the Annual Congress of the Taiwanese Diabetes Association (TDA), 23–24 March 2014, Taiwan, and the 57th Annual Meeting of the Japanese Diabetes Society (JDS), 22–24 May 2014, Osaka, Japan. In addition, these data have been published in abstract form in a supplement of Diabetologia (Diabetologia 2013; 56 (suppl 1): S371–S372 ). All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.
Conflict of interest
Takashi Kadowaki has participated on advisory panels for Takeda, Daiichi-Sankyo, Tanabe-Mitsubishi, Taisho, Boehringer Ingelheim and Novo Nordisk, has received honoraria for lectures from Boehringer Ingelheim, Daiichi-Sankyo, Tanabe-Mitsubishi, Astellas, Takeda, Kowa, AstraZeneca, Dainippon-Sumitomo, Sanwa, Taisho, Eli Lilly and Company, Kyowa Hakko Kirin, MSD, Ono, Novartis and Sanofi, research support from Chugai, MSD, Ono, Daiichi-Sankyo, Tanabe-Mitsubishi, Sanofi, AstraZeneca and Takeda, and scholarship grants from MSD, Boehringer Ingelheim, Takeda, Novo Nordisk and Terumo. Masakazu Haneda has received honoraria for lectures from Novo Nordisk, MSD, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Sanofi, Astellas, Kyowa Hakko Kirin, Kowa, Taisho, Takeda and Boehringer Ingelheim, and research support from MSD, Daiichi-Sankyo, Tanabe-Mitsubishi, Takeda, Novo Nordisk, Eli Lilly and Company, Astellas and Boehringer Ingelheim. Nobuya Inagaki has participated on advisory panels for Daiichi-Sankyo, Tanabe-Mitsubishi, Taisho and Boehringer Ingelheim, has received honoraria for lectures from MSD, Ono, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Taisho, Eli Lilly and Company, Sanofi, AstraZeneca, Astellas, Kowa, Boehringer Ingelheim, and research support from MSD, Ono, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Taisho, Eli Lilly and Company, Sanofi, AstraZeneca, Astellas, Bristol-Myers, Chugai and Boehringer Ingelheim. Yasuo Terauchi has received honoraria for lectures from MSD, Ono, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Eli Lilly and Company, Sanofi, AstraZeneca, Kowa, Takeda, Sanwa, Novo Nordisk, Shionogi, Bayer and Boehringer Ingelheim, and research support from MSD, Ono, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Eli Lilly and Company, Sanofi, AstraZeneca, Astellas, Takeda, Sanwa, Novo Nordisk, Dainippon-Sumitomo, Shionogi, Bayer, Pfizer and Boehringer Ingelheim. Atsushi Taniguchi is an employee of Boehringer Ingelheim. Kazuki Koiwai is an employee of Boehringer Ingelheim. Henning Rattunde is an employee of Boehringer Ingelheim. Hans J. Woerle is an employee of Boehringer Ingelheim. Uli C. Broedl is an employee of Boehringer Ingelheim.
Compliance with ethics guidelines
All procedures followed were in accordance with the International Conference on Harmonization Harmonized Tripartite Guideline for Good Clinical Practice, the Japanese GCP regulations (Ministry of Health and Welfare Ordinance No. 28, March 27, 1997), and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study.
Takashi Kadowaki, Masakazu Haneda and Nobuya Inagaki contributed to the implementation of clinical trial and interpretation of data, Atsushi Taniguchi, Kazuki Koiwai, Hans J. Woerle and Uli C. Broedl contributed to the study design and interpretation of data and Yasuo Terauchi and Henning Rattunde contributed to the interpretation of data. All authors were involved with drafting the article or revising it critically for important intellectual content and all authors have approved the final version to be published.
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