Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Fast track – JSH2023 OSAKA
  • Published:

Long-term effects of ipragliflozin on blood pressure in patients with type 2 diabetes: insights from the randomized PROTECT trial

Hypertension Research volume 47, pages 168–176 (2024)Cite this article

Abstract

Although previous reports have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors have a blood pressure (BP) lowering effect, relevant long-term data is limited. This study aimed to evaluate the effect of the SGLT2 inhibitor ipragliflozin on BP, and associations between BP reduction and changes in cardiometabolic variables in diabetic patients. This was a sub-analysis of the PROTECT trial, a multicenter, randomized, open-label study to assess if ipragliflozin delays carotid atherosclerosis in patients with type 2 diabetes. Participants were randomized to ipragliflozin and control groups. The primary endpoint of the present sub-analysis was the trajectory of systolic BP over 24 months. Correlations between systolic BP changes and cardiometabolic variables were also evaluated. A total of 232 eligible participants with well-balanced baseline characteristics were included in each study group. Throughout the 24-month study period, mean systolic BP was lower in the ipragliflozin group. At 24 months, a between-group difference (ipragliflozin minus control) in mean systolic BP change from baseline was −3.6 mmHg (95% confidence interval, −6.2 to −1.0 mmHg), and the reduction in systolic BP in the ipragliflozin group was consistent across subgroups examined. Changes in systolic BP significantly correlated with those in body mass index in the ipragliflozin group, while no significant correlations with other cardiometabolic variables tested were observed. In conclusion, ipragliflozin treatment was associated with BP reduction throughout the 24-month follow-up period as compared to control treatment. BP reduction correlated with weight loss, which might be one of the mechanisms for the BP lowering effect of SGLT2 inhibitors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Braunwald E. Gliflozins in the management of cardiovascular disease. N Engl J Med. 2022;386:2024–34.

    Article  CAS  PubMed  Google Scholar 

  2. McGuire DK, Shih WJ, Cosentino F, Charbonnel B, Cherney DZI, Dagogo-Jack S, et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol. 2021;6:148–58.

    Article  PubMed  Google Scholar 

  3. Nuffield Department of Population Health Renal Studies Group. SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022;400:1788–801.

    Article  Google Scholar 

  4. Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020;17:761–72.

    Article  CAS  PubMed  Google Scholar 

  5. Lopaschuk GD, Verma S. Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: a state-of-the-art review. JACC Basic Transl Sci. 2020;5:632–44.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Mazidi M, Rezaie P, Gao HK, Kengne AP. Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22,528 patients. J Am Heart Assoc. 2017;6:e004007.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Benham JL, Booth JE, Sigal RJ, Daskalopoulou SS, Leung AA, Rabi DM. Systematic review and meta-analysis: SGLT2 inhibitors, blood pressure and cardiovascular outcomes. Int J Cardiol Heart Vasc. 2021;33:100725.

    PubMed  PubMed Central  Google Scholar 

  8. Nazarzadeh M, Bidel Z, Canoy D, Copland E, Bennett DA, Dehghan A, et al. Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis. Lancet Diabetes Endocrinol. 2022;10:645–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang H, Yao G, Chen X, Ouyang J, Yang J. Ipragliflozin as an add-on therapy in type 2 diabetes mellitus patients: an evidence-based pharmacoeconomics evaluation. Diabetes Res Clin Pract. 2019;157:107867.

    Article  CAS  PubMed  Google Scholar 

  10. Alkabbani W, Gamble JM. Profile of ipragliflozin, an oral SGLT-2 inhibitor for the treatment of type 2 diabetes: the evidence to date. Drug Des Devel Ther. 2021;15:3057–69.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Tanaka A, Sata M, Okada Y, Teragawa H, Eguchi K, Shimabukuro M, et al. Effect of ipragliflozin on carotid intima-media thickness in patients with type 2 diabetes: a multicenter, randomized, controlled trial. Eur Heart J Cardiovasc Pharmacother. 2023;9:165–72.

    Article  PubMed  Google Scholar 

  12. Tanaka A, Murohara T, Taguchi I, Eguchi K, Suzuki M, Kitakaze M, et al. Rationale and design of a multicenter randomized controlled study to evaluate the preventive effect of ipragliflozin on carotid atherosclerosis: the PROTECT study. Cardiovasc Diabetol. 2016;15:133.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kishimoto S, Higashi Y, Imai T, Eguchi K, Fukumoto K, Tomiyama H, et al. Lack of impact of ipragliflozin on endothelial function in patients with type 2 diabetes: sub-analysis of the PROTECT study. Cardiovasc Diabetol. 2023;22:119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tanaka A, Imai T, Toyoda S, Sugimoto K, Yoshida R, Furuta M, et al. Long-term observation of estimated fluid volume reduction after the initiation of ipragliflozin in patients with type 2 diabetes mellitus: a sub-analysis from a randomized controlled trial (PROTECT). Diabetol Metab Syndr. 2023;15:152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res. 2019;42:1235–481.

    Article  PubMed  Google Scholar 

  16. Araki E, Goto A, Kondo T, Noda M, Noto H, Origasa H, et al. Japanese clinical practice guideline for diabetes 2019. Diabetol Int. 2020;11:165–223.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28.

    Article  CAS  PubMed  Google Scholar 

  18. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–57.

    Article  CAS  PubMed  Google Scholar 

  19. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347–57.

    Article  CAS  PubMed  Google Scholar 

  20. GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402:203–34.

    Article  Google Scholar 

  21. Sha S, Polidori D, Farrell K, Ghosh A, Natarajan J, Vaccaro N, et al. Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double-blind, crossover study. Diabetes Obes Metab. 2015;17:188–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jiang Y, Yang P, Fu L, Sun L, Shen W, Wu Q. Comparative cardiovascular outcomes of SGLT2 inhibitors in type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials. Front Endocrinol. 2022;13:802992.

    Article  Google Scholar 

  23. Maliha G, Townsend RR. SGLT2 inhibitors: their potential reduction in blood pressure. J Am Soc Hypertens. 2015;9:48–53.

    Article  CAS  PubMed  Google Scholar 

  24. Sawami K, Tanaka A, Node K. Recent understandings about hypertension management in type 2 diabetes: what are the roles of SGLT2 inhibitor, GLP-1 receptor agonist, and finerenone? Hypertens Res. 2023;46:1892–9.

    Article  CAS  PubMed  Google Scholar 

  25. Cefalu WT, Stenlöf K, Leiter LA, Wilding JP, Blonde L, Polidori D. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes. Diabetologia. 2015;58:1183–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wilcox CS. Antihypertensive and renal mechanisms of SGLT2 (sodium-glucose linked transporter 2) inhibitors. Hypertension. 2020;75:894–901.

    Article  CAS  PubMed  Google Scholar 

  27. Herat LY, Magno AL, Rudnicka C, Hricova J, Carnagarin R, Ward NC, et al. SGLT2 inhibitor-induced sympathoinhibition: a novel mechanism for cardiorenal protection. JACC Basic Transl Sci. 2020;5:169–79.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016;134:752–72.

    Article  CAS  PubMed  Google Scholar 

  29. Hu M, Cai X, Yang W, Zhang S, Nie L, Ji L. Effect of hemoglobin a1c reduction or weight reduction on blood pressure in glucagon-like peptide-1 receptor agonist and sodium-glucose cotransporter-2 inhibitor treatment in type 2 diabetes mellitus: a meta-analysis. J Am Heart Assoc. 2020;9:e015323.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shi Q, Nong K, Vandvik PO, Guyatt GH, Schnell O, Rydén L, et al. Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2023;381:e074068.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Neter JE, Stam BE, Kok FJ, Grobbee DE, Geleijnse JM. Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2003;42:878–84.

    Article  CAS  PubMed  Google Scholar 

Download references

the PROTECT investigators:

Principal Investigators Koichi Node9, Toyoaki Murohara10

Research Advisor Masafumi Kitakaze11

Steering Committee Yoshihiko Nishio12, Teruo Inoue13, Mitsuru Ohishi12, Kazuomi Kario14, Masataka Sata15, Michio Shimabukuro16, Wataru Shimizu17, Hideaki Jinnouchi18, Isao Taguchi19, Hirofumi Tomiyama20, Koji Maemura21

Executive Committee Makoto Suzuki22, Shinichi Ando23, Kazuo Eguchi24, Haruo Kamiya25, Tomohiro Sakamoto26, Hiroki Teragawa27, Mamoru Nanasato28

Data and Safety Monitoring Board Munehide Matsuhisa15, Junya Ako29, Yoshimasa Aso13, Masaharu Ishihara30, Kazuo Kitagawa31, Akira Yamashina32

Tsukuba Echo Core Laboratory. LLC Tomoko Ishizu33

Monitoring Yumi Ikehara34, Shinichiro Ueda34

Audit Team35

Data Center and Data Management Ayako Takamori36

Statistical Analysis Hisako Yoshida37, Takumi Imai38

Study Secretariat Atsushi Tanaka9

Site Investigators (duplicates excluded) Machiko Asaka9, Tetsuya Kaneko9, Masashi Sakuma13, Shigeru Toyoda13, Takahisa Nasuno13, Michiya Kageyama13, Jojima Teruo13, Iijima Toshie13, Haruka Kishi13, Hirotsugu Yamada15, Kenya Kusunose15, Daiju Fukuda15, Shusuke Yagi15, Koji Yamaguchi15, Takayuki Ise15, Yutaka Kawabata15, Akio Kuroda15, Yuichi Akasaki12, Mihoko Kurano12, Satoshi Hoshide14, Takahiro Komori14, Tomoyuki Kabutoya14, Yukiyo Ogata14, Yuji Koide21, Hiroaki Kawano21, Satoshi Ikeda21, Satoki Fukae21, Seiji Koga21, Yukihito Higashi39, Shinji Kishimoto39, Masato Kajikawa39, Tatsuya Maruhashi39, Yoshiaki Kubota17, Yoshisato Shibata40, Nehiro Kuriyama40, Ikuko Nakamura41, Kanemitsu Hironori42, Bonpei Takase43, Yuichi Orita27, Chikage Oshita27, Yuko Uchimura27, Ruka Yoshida44, Yukihiko Yoshida44, Hirohiko Suzuki44, Yasuhiro Ogura44, Mayuho Maeda44, Masaki Takenaka44, Takumi Hayashi44, Mirai Hirose44, Itaru Hisauchi19, Toshiaki Kadokami23, Ryo Nakamura23, Junji Kanda45, Kazuo Matsunaga46, Masaaki Hoshiga47, Koichi Sohmiya47, Yumiko Kanzaki47, Arihiro Koyosue48, Hiroki Uehara49, Naoto Miyagi49, Toshiya Chinen49, Kentaro Nakamura49, Chikashi Nago49, Suguru Chiba49, Sho Hatano49, Yoshikatsu Gima49, Masami Abe49, Masayoshi Ajioka50, Hiroshi Asano50, Yoshihiro Nakashima50, Hiroyuki Osanai50, Takahiro Kanbara50, Yusuke Sakamoto50, Mitsutoshi Oguri51, Shiou Ohguchi51, Kunihiko Takahara51, Kazuhiro Izumi51, Kenichiro Yasuda51, Akihiro Kudo16, Noritaka Machii16, Ryota Morimoto10, Yasuko Bando10, Takahiro Okumura10, Toru Kondo10, Shin-ichiro Miura52, Yuhei Shiga52, Joji Mirii52, Makoto Sugihara52, Tadaaki Arimura52, Junko Nakano53, Tomohiro Sakamoto26, Kazuhisa Kodama26, Nobuyuki Ohte54, Tomonori Sugiura54, Kazuaki Wakami54, Yasuhiko Takemoto55, Minoru Yoshiyama55, Taichi Shuto55, Kazuo Fukumoto55, Yosuke Okada56, Kenichi Tanaka56, Satomi Sonoda56, Akemi Tokutsu56, Takashi Otsuka56, Fumi Uemura56, Kenji Koikawa56, Megumi Miyazaki56, Maiko Umikawa56, Manabu Narisawa56, Machi Furuta57, Hiroshi Minami58, Masaru Doi59, Kazuhiro Sugimoto60, Susumu Suzuki60, Akira Kurozumi61, Kosuke Nishio61

Funding

This study was funded by Astellas Pharma Inc. Japan, and KN received the funding. The funder of the trial had no role in the study design, data collection, data analysis, data interpretation, or writing of the work.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan

    Yuichi Saito & Yoshio Kobayashi

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

    Atsushi Tanaka & Koichi Node

  3. Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan

    Takumi Imai

  4. Department of Cardiovascular Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan

    Ikuko Nakamura

  5. Department of Cardiovascular Medicine, Asahi General Hospital, Asahi, Japan

    Junji Kanda

  6. Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan

    Munehide Matsuhisa

  7. Division of Cardiology, Urasoe General Hospital, Urasoe, Japan

    Hiroki Uehara

  8. Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan

    Kazuomi Kario

  9. Saga University, Saga, Japan

    Koichi Node, Atsushi Tanaka, Machiko Asaka & Tetsuya Kaneko

  10. Nagoya University, Naogya, Japan

    Toyoaki Murohara, Ryota Morimoto, Yasuko Bando, Takahiro Okumura & Toru Kondo

  11. Hanwa Daini Senboku Hospital, Sakai, Japan

    Masafumi Kitakaze

  12. Kagoshima University, Kagoshima, Japan

    Yoshihiko Nishio, Mitsuru Ohishi, Yuichi Akasaki & Mihoko Kurano

  13. Dokkyo Medical University, Mibu, Japan

    Teruo Inoue, Yoshimasa Aso, Masashi Sakuma, Shigeru Toyoda, Takahisa Nasuno, Michiya Kageyama, Jojima Teruo, Iijima Toshie & Haruka Kishi

  14. Jichi Medical University School of Medicine, Shimotsuke, Japan

    Kazuomi Kario, Satoshi Hoshide, Takahiro Komori, Tomoyuki Kabutoya & Yukiyo Ogata

  15. Tokushima University Graduate School, Tokushima, Japan

    Masataka Sata, Munehide Matsuhisa, Hirotsugu Yamada, Kenya Kusunose, Daiju Fukuda, Shusuke Yagi, Koji Yamaguchi, Takayuki Ise, Yutaka Kawabata & Akio Kuroda

  16. Fukushima Medical University, Fukushima, Japan

    Michio Shimabukuro, Akihiro Kudo & Noritaka Machii

  17. Nippon Medical School, Tokyo, Japan

    Wataru Shimizu & Yoshiaki Kubota

  18. Jinnouchi Hospital, Kumamoto, Japan

    Hideaki Jinnouchi

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

    Isao Taguchi & Itaru Hisauchi

  20. Tokyo Medical University, Tokyo, Japan

    Hirofumi Tomiyama

  21. Nagasaki University, Nagasaki, Japan

    Koji Maemura, Yuji Koide, Hiroaki Kawano, Satoshi Ikeda, Satoki Fukae & Seiji Koga

  22. Yokohama Minami Kyosai Hospital, Yokohama, Japan

    Makoto Suzuki

  23. Saiseikai Futsukaichi Hospital, Chikushino, Japan

    Shinichi Ando, Toshiaki Kadokami & Ryo Nakamura

  24. Saitama Red Cross Hospital, Saitama, Japan

    Kazuo Eguchi

  25. Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan

    Haruo Kamiya

  26. Saiseikai Kumamoto Hospital, Kumamoto, Japan

    Tomohiro Sakamoto & Kazuhisa Kodama

  27. JR Hiroshima Hospital, Hiroshima, Japan

    Hiroki Teragawa, Yuichi Orita, Chikage Oshita & Yuko Uchimura

  28. Sakakibara Heart Institute, Fuchu, Japan

    Mamoru Nanasato

  29. Kitasato University, Sagamihara, Japan

    Junya Ako

  30. Hyogo College of Medicine, Nishinomiya, Japan

    Masaharu Ishihara

  31. Tokyo Women’s Medical University, Tokyo, Japan

    Kazuo Kitagawa

  32. Kiryu University, Midori, Japan

    Akira Yamashina

  33. Tsukuba University, Tsukuba, Japan

    Tomoko Ishizu

  34. Clinical Trial and Management Center, University of the Ryukyus Hospital, Nishihara, Japan

    Yumi Ikehara & Shinichiro Ueda

  35. Clinical Research Center, Saga University Hospital, Saga, Japan

    Ayako Takamori

  36. Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Hisako Yoshida

  37. Kobe University Hospital, Kobe, Japan

    Takumi Imai

  38. Hiroshima Universsity, Hiroshima, Japan

    Yukihito Higashi, Shinji Kishimoto, Masato Kajikawa & Tatsuya Maruhashi

  39. Miyazaki Medical Association Hospital, Miyazaki, Japan

    Yoshisato Shibata & Nehiro Kuriyama

  40. Saga-Ken Medical Centre Koseikan, Saga, Japan

    Ikuko Nakamura

  41. International University of Health and Welfare, Nasushiobara, Japan

    Kanemitsu Hironori

  42. National Defense Medical College, Tokorozawa, Japan

    Bonpei Takase

  43. Nagoya Daini Red Cross Hospital, Nagoya, Japan

    Ruka Yoshida, Yukihiko Yoshida, Hirohiko Suzuki, Yasuhiro Ogura, Mayuho Maeda, Masaki Takenaka, Takumi Hayashi & Mirai Hirose

  44. Asahi General Hospital, Asahi, Japan

    Junji Kanda

  45. Imari Arita Kyoritsu Hospital, Matsuura, Japan

    Kazuo Matsunaga

  46. Osaka Medical and Pharmaceutical University, Takatsuki, Japan

    Masaaki Hoshiga, Koichi Sohmiya & Yumiko Kanzaki

  47. Tokyo-Eki Center-Building Clinic, Tokyo, Japan

    Arihiro Koyosue

  48. Urasoe General Hospital, Urasoe, Japan

    Hiroki Uehara, Naoto Miyagi, Toshiya Chinen, Kentaro Nakamura, Chikashi Nago, Suguru Chiba, Sho Hatano, Yoshikatsu Gima & Masami Abe

  49. Tosei General Hospital, Seto, Japan

    Masayoshi Ajioka, Hiroshi Asano, Yoshihiro Nakashima, Hiroyuki Osanai, Takahiro Kanbara & Yusuke Sakamoto

  50. Kasugai Municipal Hospital, Kasugai, Japan

    Mitsutoshi Oguri, Shiou Ohguchi, Kunihiko Takahara, Kazuhiro Izumi & Kenichiro Yasuda

  51. Fukuoka University School of Medicine, Fukuoka, Japan

    Shin-ichiro Miura, Yuhei Shiga, Joji Mirii, Makoto Sugihara & Tadaaki Arimura

  52. Saiseikai Fukushima General Hospital, Fukushima, Japan

    Junko Nakano

  53. Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Nobuyuki Ohte, Tomonori Sugiura & Kazuaki Wakami

  54. Osaka City University, Osaka, Japan

    Yasuhiko Takemoto, Minoru Yoshiyama, Taichi Shuto & Kazuo Fukumoto

  55. University of Occupational and Environmental Health, Japan, Kitakyusyu, Japan

    Yosuke Okada, Kenichi Tanaka, Satomi Sonoda, Akemi Tokutsu, Takashi Otsuka, Fumi Uemura, Kenji Koikawa, Megumi Miyazaki, Maiko Umikawa & Manabu Narisawa

  56. Wakayama Medical University, Wakayama, Japan

    Machi Furuta

  57. Aidu Chuo Hospital, Aiduwakamatsu, Japan

    Hiroshi Minami

  58. Doi Naika Clinicm Kumamoto, Kumamoto, Japan

    Masaru Doi

  59. Ohta Nishinouchi Hospital, Koriyama, Japan

    Kazuhiro Sugimoto & Susumu Suzuki

  60. Wakamatsu Hospital of the University of Occupational and Environmental Health, Japan, Kitakyusyu, Japan

    Akira Kurozumi & Kosuke Nishio

Authors
  1. Yuichi Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atsushi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takumi Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ikuko Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Junji Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Munehide Matsuhisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroki Uehara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuomi Kario
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshio Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Koichi Node
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the PROTECT investigators

  • Principal Investigators

    • Koichi Node
    •  & Toyoaki Murohara

  • Research Advisor

    • Masafumi Kitakaze

  • Steering Committee

    • Yoshihiko Nishio
    • , Teruo Inoue
    • , Mitsuru Ohishi
    • , Kazuomi Kario
    • , Masataka Sata
    • , Michio Shimabukuro
    • , Wataru Shimizu
    • , Hideaki Jinnouchi
    • , Isao Taguchi
    • , Hirofumi Tomiyama
    •  & Koji Maemura

  • Executive Committee

    • Makoto Suzuki
    • , Shinichi Ando
    • , Kazuo Eguchi
    • , Haruo Kamiya
    • , Tomohiro Sakamoto
    • , Hiroki Teragawa
    •  & Mamoru Nanasato

  • Data and Safety Monitoring Board

    • Munehide Matsuhisa
    • , Junya Ako
    • , Yoshimasa Aso
    • , Masaharu Ishihara
    • , Kazuo Kitagawa
    •  & Akira Yamashina

  • Tsukuba Echo Core Laboratory. LLC

    • Tomoko Ishizu

  • Monitoring

    • Yumi Ikehara
    •  & Shinichiro Ueda
  • , Audit Team

  • Data Center and Data Management

    • Ayako Takamori

  • Statistical Analysis

    • Hisako Yoshida
    •  & Takumi Imai

  • Study Secretariat

    • Atsushi Tanaka

  • Site Investigators (duplicates excluded)

    • Machiko Asaka
    • , Tetsuya Kaneko
    • , Masashi Sakuma
    • , Shigeru Toyoda
    • , Takahisa Nasuno
    • , Michiya Kageyama
    • , Jojima Teruo
    • , Iijima Toshie
    • , Haruka Kishi
    • , Hirotsugu Yamada
    • , Kenya Kusunose
    • , Daiju Fukuda
    • , Shusuke Yagi
    • , Koji Yamaguchi
    • , Takayuki Ise
    • , Yutaka Kawabata
    • , Akio Kuroda
    • , Yuichi Akasaki
    • , Mihoko Kurano
    • , Satoshi Hoshide
    • , Takahiro Komori
    • , Tomoyuki Kabutoya
    • , Yukiyo Ogata
    • , Yuji Koide
    • , Hiroaki Kawano
    • , Satoshi Ikeda
    • , Satoki Fukae
    • , Seiji Koga
    • , Yukihito Higashi
    • , Shinji Kishimoto
    • , Masato Kajikawa
    • , Tatsuya Maruhashi
    • , Yoshiaki Kubota
    • , Yoshisato Shibata
    • , Nehiro Kuriyama
    • , Ikuko Nakamura
    • , Kanemitsu Hironori
    • , Bonpei Takase
    • , Yuichi Orita
    • , Chikage Oshita
    • , Yuko Uchimura
    • , Ruka Yoshida
    • , Yukihiko Yoshida
    • , Hirohiko Suzuki
    • , Yasuhiro Ogura
    • , Mayuho Maeda
    • , Masaki Takenaka
    • , Takumi Hayashi
    • , Mirai Hirose
    • , Itaru Hisauchi
    • , Toshiaki Kadokami
    • , Ryo Nakamura
    • , Junji Kanda
    • , Kazuo Matsunaga
    • , Masaaki Hoshiga
    • , Koichi Sohmiya
    • , Yumiko Kanzaki
    • , Arihiro Koyosue
    • , Hiroki Uehara
    • , Naoto Miyagi
    • , Toshiya Chinen
    • , Kentaro Nakamura
    • , Chikashi Nago
    • , Suguru Chiba
    • , Sho Hatano
    • , Yoshikatsu Gima
    • , Masami Abe
    • , Masayoshi Ajioka
    • , Hiroshi Asano
    • , Yoshihiro Nakashima
    • , Hiroyuki Osanai
    • , Takahiro Kanbara
    • , Yusuke Sakamoto
    • , Mitsutoshi Oguri
    • , Shiou Ohguchi
    • , Kunihiko Takahara
    • , Kazuhiro Izumi
    • , Kenichiro Yasuda
    • , Akihiro Kudo
    • , Noritaka Machii
    • , Ryota Morimoto
    • , Yasuko Bando
    • , Takahiro Okumura
    • , Toru Kondo
    • , Shin-ichiro Miura
    • , Yuhei Shiga
    • , Joji Mirii
    • , Makoto Sugihara
    • , Tadaaki Arimura
    • , Junko Nakano
    • , Tomohiro Sakamoto
    • , Kazuhisa Kodama
    • , Nobuyuki Ohte
    • , Tomonori Sugiura
    • , Kazuaki Wakami
    • , Yasuhiko Takemoto
    • , Minoru Yoshiyama
    • , Taichi Shuto
    • , Kazuo Fukumoto
    • , Yosuke Okada
    • , Kenichi Tanaka
    • , Satomi Sonoda
    • , Akemi Tokutsu
    • , Takashi Otsuka
    • , Fumi Uemura
    • , Kenji Koikawa
    • , Megumi Miyazaki
    • , Maiko Umikawa
    • , Manabu Narisawa
    • , Machi Furuta
    • , Hiroshi Minami
    • , Masaru Doi
    • , Kazuhiro Sugimoto
    • , Susumu Suzuki
    • , Akira Kurozumi
    •  & Kosuke Nishio

Corresponding authors

Correspondence to Atsushi Tanaka or Koichi Node.

Ethics declarations

Conflict of interest

YS received honoraria from Daiichi Sankyo. AT received honoraria from Boehringer Ingelheim Japan and research funding from GlaxoSmithKline, Takeda, Bristol-Myers Squibb, and Novo Nordisk. TI received lecture fees from JCR Pharmaceuticals and Kyowa Kirin and outsourcing fees from the Organization for Clinical Medicine Promotion. MM received honoraria from Sanofi, Eli Lilly Japan, Novo Nordisk Pharma, Abbott Japan, Sumitomo Pharma, Kyowa Kirin, Nippon Boehringer Ingelheim, and Orizuru Therapeutics, research funding from Novo Nordisk Pharma, and subsidies or donations from Sysmex and Nissui. KK reports lecture fees from Otsuka Pharmaceuticals, Daiichi Sankyo, Novartis Pharma, and Viatris, research grant from Otsuka Pharmaceuticals, Sanwa Kagaku Kenkyusho, Daiichi Sankyo, Taisho Pharmaceutical, Sumitomo Pharma, Takeda Pharmaceuticals, Mitsubishi Tanabe Pharma, Boehringer Ingerheim Japan, and Mochida Pharmaceuticals, and consulting fees from Sanwa Kagaku Kenkyusho, Mochida Pharmaceuticals and is an advisory board member of Daiichi Sankyo and Novartis Pharma. YK received honoraria from Astellas, AstraZeneca, Boehringer Ingelheim, and Daiichi-Sankyo and research grant from Boehringer Ingelheim and Daiichi-Sankyo. KN has received honoraria from AstraZeneca, Bayer Yakuhin, Boehringer Ingelheim Japan, Daiichi Sankyo, Eli Lilly Japan, Kowa, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma, Novo Nordisk Pharma, Ono Pharmaceutical, Otsuka, and Takeda Pharmaceutical, research grant from Asahi Kasei, Astellas, Boehringer Ingelheim Japan, Fuji Yakuhin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Novartis Pharma, and Teijin Pharma, and scholarship from Bayer Yakuhin, Medtronic, Teijin Pharma. All other authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saito, Y., Tanaka, A., Imai, T. et al. Long-term effects of ipragliflozin on blood pressure in patients with type 2 diabetes: insights from the randomized PROTECT trial. Hypertens Res 47, 168–176 (2024). https://doi.org/10.1038/s41440-023-01494-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-023-01494-6

Keywords

This article is cited by

Search

Advanced search

Quick links