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  • Brief Communication
  • Special Issue: Current evidence and perspectives for hypertension management in Asia
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Blood pressure reduction with empagliflozin in Japanese patients with type 2 diabetes and cardiovascular diseases: a post-hoc sub-analysis of the placebo-controlled randomized EMBLEM trial

Hypertension Research volume 47, pages 2295–2302 (2024)Cite this article

A Comment to this article was published on 04 July 2024

Abstract

Detailed effect of sodium-glucose cotransporter 2 inhibitors on blood pressure (BP) in Japanese patients with type 2 diabetes (T2D) at a high risk of cardiovascular disease (CVD) is not fully understood. In this post-hoc sub-analysis of placebo-controlled randomized EMBLEM trial for Japanese patients with T2D and CVD, 105 participants (empagliflozin N = 52, placebo N = 53) were included, and office systolic/diastolic BPs and mean arterial pressure (MAP) over 24 weeks were estimated using mixed-effects models for repeated measures. Empagliflozin therapy, compared to placebo, reduced systolic/diastolic BPs (mean group difference in change from baseline to week 24; −5.9 [95% confidence interval (CI), −10.4 to −1.4] mmHg/−2.9 [95% CI, −6.2 to 0.4] mmHg) and MAP ( − 3.8 [95% CI, −7.0 to −0.7] mmHg). The systolic BP reduction was almost consistent across differing background clinical characteristics and usage status of anti-hypertensive medications.

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Acknowledgements

The authors thank all participants, investigators, board members, and medical staff involved in the EMBLEM trial.

on behalf of the EMBLEM Investigators

Junya Ako12, Hirohisa Amano13, Itaru Hisauchi14, Yumi Ikehara15, Hideaki Jinnouchi16, Yoshiyuki Kawano17, Kazuo Kimura18, Akira Kurozumi19, Takaaki Kusumoto20, Noritaka Machii21, Tatsuya Maruhashi22, Yasushi Matsuzawa18, Hirofumi Misu23, Manabu Narisawa19, Tsuguhito Ota23, Jun-ichi Oyama24, Masashi Sakuma13, Kazuki Shiina25, Kosuke R. Shima23, Seigo Sugiyama16, Kunihiro Suzuki13, Naohiko Takahashi26, Yasuhiko Takemoto27, Yumie Takeshita23, Hiroshi Tamaki28, Kenichi Tanaka19, Akira Tamura17, Keiichi Torimoto19, Minako Yamaoka-Tojo12, Hiroki Uehara29, Fumi Uemura19, Ken Yamakawa30, Kunio Yufu26

Funding

The EMBLEM trial was funded by Boehringer Ingelheim and Eli Lilly and Company. The funders of the trial had no role in the study design, data collection, data analysis, or data interpretation, or writing of the paper. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to Boehringer Ingelheim substances, as well as intellectual property considerations.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Saga University, Saga, Japan

    Atsushi Tanaka & Koichi Node

  2. Department of Diabetes, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima, Japan

    Michio Shimabukuro

  3. Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima, Japan

    Hiroki Teragawa

  4. Department of Medical Statistics, Osaka Metropolitan University, Osaka, Japan

    Hisako Yoshida

  5. First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyusyu, Japan

    Yosuke Okada

  6. Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan

    Toshinari Takamura

  7. The Department of Cardiology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan

    Isao Taguchi

  8. Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Mibu, Japan

    Shigeru Toyoda

  9. Department of Cardiology, Tokyo Medical University, Tokyo, Japan

    Hirofumi Tomiyama

  10. Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan

    Shinichiro Ueda

  11. Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Yukihito Higashi

  12. Kitasato University School of Medicine, Sagamihara, Japan

    Junya Ako & Minako Yamaoka-Tojo

  13. Dokkyo Medical University School of Medicine, Mibu, Japan

    Hirohisa Amano, Masashi Sakuma & Kunihiro Suzuki

  14. Dokkyo Medical University Saitama Medical Center, Saitama, Japan

    Itaru Hisauchi

  15. University of the Ryukyus Hospital, Nishihara, Japan

    Yumi Ikehara

  16. Jinnouchi Hospital, Kumamoto, Japan

    Hideaki Jinnouchi & Seigo Sugiyama

  17. Hetsugi Hospital, Oita, Japan

    Yoshiyuki Kawano & Akira Tamura

  18. Yokohama City University Medical Center, Yokohama, Japan

    Kazuo Kimura & Yasushi Matsuzawa

  19. University of Occupational and Environmental Health, Kitakyushu, Japan

    Akira Kurozumi, Manabu Narisawa, Kenichi Tanaka, Keiichi Torimoto & Fumi Uemura

  20. Izumi General Medical Center, Izumi, Japan

    Takaaki Kusumoto

  21. Fukushima Medical University, Fukushima, Japan

    Noritaka Machii

  22. Hiroshima University, Hiroshima, Japan

    Tatsuya Maruhashi

  23. Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan

    Hirofumi Misu, Tsuguhito Ota, Kosuke R. Shima & Yumie Takeshita

  24. Saga University, Saga, Japan

    Jun-ichi Oyama

  25. Tokyo Medical University, Tokyo, Japan

    Kazuki Shiina

  26. Oita University Faculty of Medicine, Yufu, Japan

    Naohiko Takahashi & Kunio Yufu

  27. Osaka City University Graduate School of Medicine, Osaka, Japan

    Yasuhiko Takemoto

  28. Well-Life Clinic, Chatan, Japan

    Hiroshi Tamaki

  29. Urasoe General Hospital, Urasoe, Japan

    Hiroki Uehara

  30. Chubu Tokushukai Hospital, Kitanakagusuku, Japan

    Ken Yamakawa

Authors
  1. Atsushi Tanaka
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  2. Michio Shimabukuro
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  3. Hiroki Teragawa
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  4. Hisako Yoshida
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  5. Yosuke Okada
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  6. Toshinari Takamura
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  7. Isao Taguchi
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  8. Shigeru Toyoda
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  9. Hirofumi Tomiyama
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  10. Shinichiro Ueda
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  11. Yukihito Higashi
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  12. Koichi Node
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Consortia

on behalf of the EMBLEM Investigators

  • Junya Ako
  • , Hirohisa Amano
  • , Itaru Hisauchi
  • , Yumi Ikehara
  • , Hideaki Jinnouchi
  • , Yoshiyuki Kawano
  • , Kazuo Kimura
  • , Akira Kurozumi
  • , Takaaki Kusumoto
  • , Noritaka Machii
  • , Tatsuya Maruhashi
  • , Yasushi Matsuzawa
  • , Hirofumi Misu
  • , Manabu Narisawa
  • , Tsuguhito Ota
  • , Jun-ichi Oyama
  • , Masashi Sakuma
  • , Kazuki Shiina
  • , Kosuke R. Shima
  • , Seigo Sugiyama
  • , Kunihiro Suzuki
  • , Naohiko Takahashi
  • , Yasuhiko Takemoto
  • , Yumie Takeshita
  • , Hiroshi Tamaki
  • , Kenichi Tanaka
  • , Akira Tamura
  • , Keiichi Torimoto
  • , Minako Yamaoka-Tojo
  • , Hiroki Uehara
  • , Fumi Uemura
  • , Ken Yamakawa
  •  & Kunio Yufu

Corresponding authors

Correspondence to Atsushi Tanaka or Koichi Node.

Ethics declarations

Conflict of interest

A.T. received honoraria from Nippon Boehringer Ingelheim and Mochida and research funding from GlaxoSmithKline, Takeda, Bristol-Myers Squibb, and Novo Nordisk Pharma. M.S. received honorarium and an endowed chair from Boehringer Ingelheim. H.Te. received lecture fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kowa, Takeda, Mitsubishi Tanabe, and Sanwa Kagaku Kenkyusyo. Y.O. received lecture fees from MSD, Mitsubishi Tanabe, Novo Nordisk Pharma, Eli Lilly Japan, Novartis Pharma, Kissei, Kowa, and Sumitomo Pharma and research fund from Kissei. T.T. received lecture fees from Kowa and Taisho and research grants from Kowa and Taisho. S.T. received honoraria from Daiichi Sankyo, AstraZeneca, Bayer, Nippon Boehringer Ingelheim, TSUMURA, and Novo Nordisk Pharma. Y.H. received grants from Mitsubishi Tanabe Pharma Corporation, Teijin Pharma Limited, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corporation, Sanofi Kabushiki Kaisya, AstraZeneca Kabushiki Kaisya, Kyowa Hakko Kirin Company Limited, Takeda Pharmaceutical Company Limited, Astellas Pharma Incorporated, Daiichi Sankyo Company Limited, Mochida Pharmaceutical Company Limited, Nihon Kohden Corporation, Shionogi Company Limited, Nippon Sigmax Company Limited, Sanwa Kagaku Kenkyusho Company Limited, Unex Corporation, and Kao Corporation, and honoraria from Radiometer Limited, Omron Corporation, Sumitomo Dainippon Pharma Company Limited, Otsuka Pharmaceutical Company Limited, Torii Pharmaceutical Company Limited, Kowa Company Limited, Fujiyakuhin Company Limited, Amgen Astellas BioPharma Kabushiki Kaisya, Nippon Shinyaku Company Limited, Itamar Medical Limited, Bayer Holding Limited, Eli Lilly Kabushiki Kaisya, and Ono Pharmaceutical Company Limited. K.N. received honoraria from AstraZeneca, Bayer Yakuhin, Nippon Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly Japan, Kowa, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma, Novo Nordisk Pharma, Ono Pharmaceutical, Otsuka, and Takeda Pharmaceutical, research grants from Asahi Kasei, Astellas, Nippon Boehringer Ingelheim, Fuji Yakuhin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Novartis Pharma, and Teijin Pharma, and scholarship from Bayer Yakuhin, Medtronic, and Teijin Pharma. Other authors declare no competing interests.

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Tanaka, A., Shimabukuro, M., Teragawa, H. et al. Blood pressure reduction with empagliflozin in Japanese patients with type 2 diabetes and cardiovascular diseases: a post-hoc sub-analysis of the placebo-controlled randomized EMBLEM trial. Hypertens Res 47, 2295–2302 (2024). https://doi.org/10.1038/s41440-024-01725-4

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  • DOI: https://doi.org/10.1038/s41440-024-01725-4

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