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Empagliflozin Monotherapy in Japanese Patients with Type 2 Diabetes Mellitus: a Randomized, 12-Week, Double-Blind, Placebo-Controlled, Phase II Trial

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Abstract

Introduction

This study was designed to determine the efficacy and tolerability of empagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods

Patients with glycosylated hemoglobin (HbA1c) ≥7.0–≤10% were randomized via an interactive web response system, and treated double-blind with empagliflozin 5, 10, 25, 50 mg, or placebo once daily for 12 weeks. The primary endpoint was change from baseline in HbA1c at week 12. Other endpoints included percentage of patients with HbA1c <7.0% and changes from baseline in fasting plasma glucose (FPG), body weight, and systolic blood pressure (SBP) at week 12.

Results

A total of 547 patients were randomized and treated with empagliflozin 5 mg (n = 110), 10 mg (n = 109), 25 mg (n = 109), 50 mg (n = 110), or placebo (n = 109) for 12 weeks. Adjusted mean [95% confidence interval (CI)] differences vs. placebo in changes from baseline in HbA1c were −0.72% (−0.87, −0.57) with empagliflozin 5 mg, −0.70% (−0.85, −0.55) with 10 mg, −0.95% (−1.10, −0.80) with 25 mg, and −0.91 (−1.06, −0.76) with 50 mg (all p < 0.001). More patients with HbA1c ≥7.0% at baseline reached HbA1c <7.0% with empagliflozin (19–33%) than placebo (3%). Compared with placebo, empagliflozin reduced FPG, body weight (p < 0.001 for all doses for both endpoints) and SBP (p = 0.001, p = 0.014 and p = 0.003 for empagliflozin 10, 25, and 50 mg, respectively). Adverse events were reported by 42% of patients receiving placebo and 33–38% of patients receiving empagliflozin. There were few reports of confirmed hypoglycemic adverse events or events consistent with urinary tract infection or genital infection in any treatment group.

Conclusions

Empagliflozin monotherapy for 12 weeks in Japanese patients with T2DM reduced HbA1c, FPG, body weight and SBP, and was well tolerated.

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Acknowledgments

This study was funded by Boehringer Ingelheim, Ingelheim, Germany and Eli Lilly, Indianapolis, USA. Page processing charges for this manuscript were covered by Boehringer Ingelheim, Ingelheim, Germany. Medical writing assistance was provided by Clare Ryles and Elizabeth Ng of Fleishman-Hillard Group Ltd. and funded by Boehringer Ingelheim, Ingelheim, Germany. All named authors meet the 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. These data have been presented in poster format at the 73rd Scientific Session of the American Diabetes Association, June 21–25, 2013, Chicago, USA, and at the 57th Annual Meeting of the Japan Diabetes Society, May 22–24, 2014, Osaka, Japan. These data have been published in abstract form in a supplement of Diabetes (Diabetes 2013; 62 (suppl 1): A297–A298).

Conflict of interest

Takashi Kadowaki has received honoraria for lectures from MSD, Ono, Novartis and Sanofi, grants/research support from Chugai, and scholarship grants from MSD and Boehringer Ingelheim. Masakazu Haneda has received honoraria for lectures from MSD, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Sanofi, Astellas, Kowa, Taisho and Boehringer Ingelheim, and research support from MSD, Daiichi-Sankyo, Tanabe-Mitsubishi, Eli Lilly, 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, Tanabe-Mitsubishi, Eli Lilly, Sanofi, Astra Zeneca, Astellas, Kowa, Boehringer Ingelheim, and has received research support from MSD, Ono, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Eli Lilly, Sanofi, Astra Zeneca, Astellas, Bristol-Myers Squibb, Chugai and Boehringer Ingelheim. Yasuo Terauchi has received honoraria for lectures from MSD, Ono, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Eli Lilly, Sanofi, Astra Zeneca, Kowa and Boehringer Ingelheim, and scholarship grants from MSD, Ono, Novartis, Daiichi-Sankyo, Tanabe-Mitsubishi, Eli-Lilly, Sanofi, Astra Zeneca, Astellas and Boehringer Ingelheim. These companies are involved in the development and/or distribution of SGLT2 inhibitors. 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 ethical standards of the responsible committee on human experimentation (institutional and national), and with the Helsinki Declaration of 1975, as revised in 2000 and 2008, and in accordance with the International Conference on Harmonization Harmonized Tripartite Guideline for Good Clinical Practice, and the Japanese Good Clinical Practice regulations (Ministry of Health and Welfare Ordinance No. 28, March 27, 1997). Informed consent was obtained from all patients for being included in the study. The study was approved by respective Institutional Review Boards and Competent Authorities according to national and international regulations.

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Authors and Affiliations

  1. Clinical Development and Medical Affairs TA-Diabetes, Nippon Boehringer Ingelheim Co., Ltd., Think Park Tower, 2-1-1 Osaki, Shinagawa-ku, Tokyo, 141-6017, Japan

    Atsushi Taniguchi & Kazuki Koiwai

  2. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan

    Takashi Kadowaki

  3. Department of Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan

    Masakazu Haneda

  4. Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaramachi, Sakyo-ku, Kyoto, 606-8507, Japan

    Nobuya Inagaki

  5. Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Kanagawa, 236-0004, Japan

    Yasuo Terauchi

  6. Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216, Ingelheim, Germany

    Henning Rattunde, Hans J. Woerle & Uli C. Broedl

Authors
  1. Takashi Kadowaki
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  2. Masakazu Haneda
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  3. Nobuya Inagaki
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  4. Yasuo Terauchi
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  6. Kazuki Koiwai
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  7. Henning Rattunde
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  8. Hans J. Woerle
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  9. Uli C. Broedl
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Corresponding author

Correspondence to Kazuki Koiwai.

Additional information

Trial registration: ClinicalTrials.gov #NCT01193218.

On behalf of the EMPA-REG DOSEJAPAN™ trial investigators.

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Kadowaki, T., Haneda, M., Inagaki, N. et al. Empagliflozin Monotherapy in Japanese Patients with Type 2 Diabetes Mellitus: a Randomized, 12-Week, Double-Blind, Placebo-Controlled, Phase II Trial. Adv Ther 31, 621–638 (2014). https://doi.org/10.1007/s12325-014-0126-8

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  • DOI: https://doi.org/10.1007/s12325-014-0126-8

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