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Dipeptidyl peptidase-4 inhibitors reduce the incidence of first cardiovascular events in Japanese diabetic patients

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Abstract

Background

Dipeptidyl Peptidase-4 (DPP-4) inhibitors do not suppress cardiovascular events in diabetic patients with a history of cardiovascular disease. However, the effect of DPP-4 inhibitors on cardiovascular events in Japanese diabetic patients is unclear. Therefore, we investigated whether DPP-4 inhibitors alter the incidence of cardiovascular events in Japanese diabetic patients without a history of cardiovascular events.

Methods

The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study conducted from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2019. Patients who had had a cardiovascular event by the 2013 follow-up were excluded from the study. JPAD patients were divided into a DPP-4 group and a non-DPP-4 group based on whether they were taking DPP-4 inhibitors at the 2013 follow-up because few patients took DPP-4 inhibitors before 2013. We investigated the incidence of cardiovascular events consisting of coronary events, cerebrovascular events, heart failure requiring hospitalization, and aortic and peripheral vascular disease in 1099 JPAD patients until 2019.

Results

During the observation period from 2013 to 2019, 37 (7%) first cardiovascular events occurred in the DPP-4 group (n = 518) and 66 (11%) in the non-DPP-4 group (n = 581). The incidence of cardiovascular events was significantly lower in the DPP-4 group than in the non-DPP-4 group (Log-Rank P = 0.0065). Cox proportional hazards model analysis revealed that the use of DPP-4 inhibitors (hazard ratio 0.65; 95% confidence interval 0.43–0.98; P = 0.038) was an independent factor after adjustment for age ≥ 65 years, hypertension, statin usage, and insulin usage.

Conclusions

Our findings have demonstrated that the use of DPP-4 inhibitors may be associated with a reduced incidence of first cardiovascular events in Japanese diabetic patients. The results require confirmation in randomized controlled trials.

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Data availability

The JPAD study is an ongoing cohort and data cannot be provided.

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Acknowledgements

The authors thank M. Ohtorii (Institute for Clinical Effectiveness, Kyoto, Japan) for her roles in data management and statistical analyses. The authors also thank M. Aoyama (Kumamoto University), Y. Wada, Y. Kamada, and M. Miyagawa (Nara Medical University) for their secretarial work. A part of data of the manuscript was presented in American Heart Association Scientific Sessions 2021. We thank all members of the JPAD investigators for data collection: Kimiaki Miwa (Aiiku Hospital); Kazunobu. Akahoshi (Akahoshi Clinic); Kenji Misumi (Akita Hospital); Haruo Araki (Araki Heart Clinic); Yutaka Mitsudo (Arao Central Hospital); Norifumi Kondo (Asahikawa Cardiovascular Clinic); Kenichi Ashihara (Ashihara Clinic); Shinya Yumoto (Aso Medical Center); Masashi Horimoto (Chitose City Hospital); Osamu Doi (Doi Cardiovascular Clinic); Kenichi Doijiri (Doijiri Clinic); Ryo Fukami (Fukami Clinic); Michio Shimabukuro (Fukushima Medical University); Genshi Egusa (Genshi Egusa Clinic); Kazuo Goto (Goto Clinic); Yoichi Hanaoka (Hanaoka Cardiovascular Clinic); Yoshihiro Kimura (Hanazono Medical Clinic); Yoshikuni Haraguchi, and Osamu Haraguchi (Haraguchi Gastroenterology Clinic); Atsushi Hasegawa (Hasegawa Medicine Clinic); Yoshiko Shioya, and Yosuke Shioya (Hinohikari Clinic); Eiitiro Tanaka, and Kazuhiko Yamada (Hitoyoshi internal Hospital); Toshiya Atsumi (Hokkaido University Hospital); Satoshi Tanazawa (Hokusei Hospital); Yutaka Horio (Horio Internal Medicine Clinic); Seishi Ichihara (Ichihara Clinic); Isao Yasuda (Iinan Hospital); Tsuneo Ikeda (Ikeda Internal Medical Clinic); Makoto Ikemura (Ikemura medical Clinic); Chieko Imamoto (Imamoto Clinic); Yoshihisa Iseri (Iseri Internal Medicine Clinic); Ken Iwai (Iwai Clinic); Shinya Okamoto (Iwasaki Hospital); Seigo Sugiyama (Jinnouchi Hospital); Masanori Kamura (Kamura Clinic); Hirofumi Kan (Kankaimeido Clinic); Mayumi Kiyota (Kasuga Clinic); Kyousuke Kawamura (Kawamura Internal Medicine Clinic); Takashi Ono (Kimio Ono Clinic); Takeshi Koga (Koga Clinic); Etsuo Kinuwaki, Hiromichi Naito, and Kazuo Kozuma (Konan Hospital); Kiyotaka Kudou (Kudou Internal Medicine ); Yasuhiro Morikami (Kumamoto City Hospital); Hirofumi Yasue, and Yuji Mizuno (Kumamoto Kinoh Hospital); Hisao Fujimoto (Kumamoto Onjyaku Hospital); Kozaburo Matsuyama (Kumamoto Rehabilitation Hospital); Hiromi Fujii (Kumamoto Shinto General Hospital); Syuichi Kamijikkoku (Kumamoto Takumadai Hospital); Tetsuo Kuwahara (Kuwahara Medical Clinic); Kyoji Takaoka (Kyushu Memorial Hospital); Kazuo Machii (Machii Cardiovascular Clinic); Kazutaka Maeda (Maeda Internal medical Clinic); Keiji Mahara (Mahara Internal Medicine Clinic); Akira Maki (Maki Cardiovascular Clinic); Naoki Manda (Manda Memorial Hospital); Kousuke Marutsuka, Naoki Sameshima, and Toshihiro Gi (Masuda Hospital); Terufumi Matsunaga (Matsunaga Cardiovascular Hospital); Syuichi Matsuo (Matsuo Clinic); Hiroto Okubo (Miike Hospital); Fuyuki Minagawa (Minagawa Internal Medicine Clinic); Kotaro Minoda (Minoda Cardiovascular Clinic); Junichi Miyata (Miyata Internal Medicine Clinic); Takeshi Matsuo (Miyazaki Social Insurance Hospital); Sueo Momosaki (Momosaki Internal Medicine Clinic); Tetsuo Munakata (Munakata Hospital); Tomoki Nakamura (Nakamura Clinic); Hisatoshi Nagano, Kazuto Goshi, and Keisuke Sugimoto (Namino Clinic); Shojiro Naomi (Naomi medicinal Clinic); Toshiaki Nasu (Nasu Internal Medicine Clinic); Hiroyuki Tanaka (Niko Clinic); Ryuji Sonoda (Nishimura Internal Medicine and Neurosurgery Hospital); Keizo Kajiwara (Obiyama Central Hospital); Takafumi Odo (Odo Clinic); Hirofumi Ogata (Ogata Internal Medicine Clinic); Masayuki Ogihara (Ogihara Naika Clinic); Tateo Ogura (Ogura Internal Medicine Clinic); Keishiro Oka (Oka Clinic); Eiji Kawashima (Onishi Hospital); Eiji Oshima (Oshima Medical Clinic); Ken Ozaki (Ozaki Clinic); Seiji Ozawa (Ozawa Clinic); Hiroyuki Shono (Saiseikai Misumi Hospital); Yasuhiro Sakamoto (Sakamoto Cardiovascular Clinic ); Nobuko Sakurai (Sakurai Cardiovascular Clinic); Chikashi Wakabayashi (Sapporo cardiovascular Hospital); Tomohiro Sawada (Sawada Internal Medicine Clinic); Junji Shibata (Shibata Gastroenterology Clinic); Hisashi Shimono (Shimono Cardiovascular Clinic); Akihiro Iemura (Shinmachi Iemura Clinic); Akira Matsutani (Shunan City Shinnanyo Hospital); Hisakazu Suefuji (Suefuji Cardiovascular Clinic); Hiromichi Sugiyama (Sugiyama Clinic); Jun Hokamaki, and Kenichi Komori (Tamana Central Hospital); Yoshimi Kinoshita (Tanimura Hospital); Hironori Murakami (Teinekeijinkai Hospital); Jun Hashiguchi, Yasuhiro Hashiguchi (Tempozan Naika Medical Clinic); Koryo Sawai (Terada Hospital); Atuko Hifumi (Terao Hospital); Koji Seo (Tochigi Public Health Service); Masamitsu Toihata (Toihata Internal Medicine Clinic); Koji Tokube (Tokube Internal Medicine Clinic); Hiroshi Ogawa (Tokyo Women's Medical University Hospital); Fumishi Tomita (Tomita Medical Clinic); Madoka Taguchi (Toshiba General Hospital); Toshio Tsubokura (Tsubokura Clinic); Tatsuaki Tsuchiya (Tsuchiya Clinic); Kaoru Tsuda (Tsuda Kaoru Clinic); Ryuichiro Tsurusaki (Tsurusaki Internal Medicine Clinic); Kenji Obata (Tsuruta Hospital); Katumi Watanabe, and Raisuke Hayasida (Ubuyamamura Clinic); Yutaka Ishibashi (West Shimane Medical and Welfare Center); Yoshiaki Osamura (Yamada Heart Clinic); Yoshito Yamanaka (Yamanaka Clinic); Kazuhiro Sonoda, and Taisuke Iwaoka (Yatsuda Hospital); Hiromitsu Yokota (Yokota Cardiovascular Clinic); Motoki Yoshinari (Yosinari Surgery and Internal Medicine Clinic); Nanami Abe (Abe Clinic); Noriaki Ando (Ando Medical Clinic); Hiroshi Bando (Bando Clinic); Takeshi Takami (Clinic Jingumae); Michiaki Doi (Doi Clinic); Yoshihiro Fujii (Fujii Naika Clinic); Masahiro Fukuda (Fukuda Clinic); Yoshiaki Fukuoka (Fukuoka Clinic); Masayoshi Hamano, and Minoru Takaoka (Hamano Clinic); Hiromi Hasegawa (Hasegawa Clinic); Ikuo Yabuta (Heart Land Shigisan Hospital); Kenshi Higami, and Satomi Higami (Higami Hospital); Akiko Yasuno, and Yuriko Fujinaga (Higashiyama Takeda Hospital); Yoko Onishi (Higuchi Clinic); Katsutoshi Yoshimura, Shigetoshi Minami, and Takao Nakashima (Hirao Hospital); Hiroaki Horie (Horie Clinic); Kazuko Horii (Horii Naika Clinic); Norihiko Matsumura (Horii Clinic); Tetsuo Ikuno (Ikuno Clinic); Yoshiyuki Katsuyama (Katsuyama Naika Clinic); Shiro Uemura (Kawasaki Medical School Hospital); Masao Kikukawa (Kikukawa Clinic); Masao Kanauchi (Kio University); Hideshi Kuzuya, and Arata Iwasaki (Kousekai Clinic); Takehiko Koutani (Koutani Clinic); Hisaharu Makino (Makino Clinic); Hiroshi Miki (Miki Clinic); Susumu Misugi (Misugi Clinic); Masaki Naito, and Masatoshi Naito (Naito Hospital); Yukitaka Nakano (Nakano Clinic); Akira Nakatani (Nakatani Clinic); Fumihiko Nakatani (Nakatani Naika Clinic); Manabu Horii, and Matahiro Yabuta (Nara City Hospital); Ayako Seno, Hiroyuki Kawata, Kenichi Samejima, Kenji Onoue, Rika Kawakami, Tomoya Nakano, Tomoya Ueda, Tsunenari Soeda, and Yoko Kita (Nara Medical University); Fumitaka Inoue (Nara Prefecture General Medical Center); Shigeru Yamano (Nara Prefecture General Rehabilitation Center); Hajime Iwama, Hirokazu Sakan, Megumi Suzuki, Tadashi Kagoshima, Takehito Nakai, Toshio Hashimoto, Yoshiharu Nishitani, and Yoshiyuki Kobayashi (Nara Prefecture Western Medical Center); Koichi Hoda (Nara Seibu Hospital); Junko Uejima, Yoshinobu Morikawa, and Takahiro Kawano (Nara South Medical Center); Hideki Yamada (Nijo Ekimae Clinic); Kazuo Nishimoto (Nishimoto Medical Clinic); Kyouyuki Ohsumi (Ohsumi Naika Clinic); Nobushige Ote (Ote Naika Clinic); Akiko Oya (Oya Clinic); Kimiaki Nishiura (Oyodo Hospital); Joji Masuda, Keiichiro Ban, and Yusuke Kyoda (Saiseikai Gose Hospital); Izumi Sawada, and Yoko Sawada (Sawada Hospital); Koichi Okada (Sawai Hospital); Akihiro Yazaki, Masakazu Hanatani (Shiraniwa Hospital); Toshio Sutani (Sutani Clinic); Yuko Hiramori (Takanohara Suzuran Clinic); Yuya Tanaka (Tanaka Naika Clinic); Toshiro Igaki, and Yukio Tomioka (Tomioka Naika Clinic); Hideo Shiiki, Kiyotaka Sugihara, Motomu Hayashi, Yasunobu Sasaki, and Yasuo Matsukura (Uda City Hospital); Michiaki Ueda (Ueda Clinic); Masakuni Ueyama (Ueyama Clinic); Hideto Uyama (Uyama Clinic); Hiroharu Yamada (Yamada Clinic); Kenichi Yamaga (Yamaga Clinic); Tamio Nakajima (Yamatokashihara Hospital); Kazumi Yoshimoto (Yoshimoto Clinic); Midori Yoshimura (Yoshimura Clinic).

Kimiaki Miwa, Kazunobu Akahoshi, Kenji Misumi, Haruo Araki, Yutaka Mitsudo, Norifumi Kondo, Kenichi Ashihara, Shinya Yumoto, Masashi Horimoto, Osamu Doi, Kenichi Doijiri, Ryo Fukami, Michio Shimabukuro, Genshi Egusa, Kazuo Goto, Yoichi Hanaoka, Yoshihiro Kimura, Yoshikuni Haraguchi, Osamu Haraguchi, Atsushi Hasegawa, Yoshiko Shioya, Yosuke Shioya, Eiitiro Tanaka, Kazuhiko Yamada, Toshiya Atsumi, Satoshi Tanazawa, Yutaka Horio, Seishi Ichihara, Isao Yasuda, Tsuneo Ikeda, Makoto Ikemura, Chieko Imamoto, Yoshihisa Iseri, Ken Iwai, Shinya Okamoto, Seigo Sugiyama, Masanori Kamura, Hirofumi Kan, Mayumi Kiyota, Kyousuke Kawamura, Takashi Ono, Takeshi Koga, Etsuo Kinuwaki, Hiromichi Naito, Kazuo Kozuma, Kiyotaka Kudou, Yasuhiro Morikami, Hirofumi Yasue, Yuji Mizuno, Hisao Fujimoto, Kozaburo Matsuyama, Hiromi Fujii, Syuichi Kamijikkoku, Tetsuo Kuwahara, Kyoji Takaoka, Kazuo Machii, Kazutaka Maeda, Keiji Mahara, Akira Maki, Naoki Manda, Kousuke Marutsuka, Naoki Sameshima, Toshihiro Gi, Terufumi Matsunaga, Syuichi Matsuo, Hiroto Okubo, Fuyuki Minagawa, Kotaro Minoda, Junichi Miyata, Takeshi Matsuo, Sueo Momosaki, Tetsuo Munakata, Tomoki Nakamura, Hisatoshi Nagano, Kazuto Goshi, Keisuke Sugimoto, Shojiro Naomi, Toshiaki Nasu, Hiroyuki Tanaka, Ryuji Sonoda, Keizo Kajiwara, Takafumi Odo, Hirofumi Ogata, Masayuki Ogihara, Tateo Ogura, Keishiro Oka, Eiji Kawashima, Eiji Oshima, Ken Ozaki, Seiji Ozawa, Hiroyuki Shono, Yasuhiro Sakamoto, Nobuko Sakurai, Chikashi Wakabayashi, Tomohiro Sawada, Junji Shibata, Hisashi Shimono, Akihiro Iemura, Akira Matsutani, Hisakazu Suefuji, Hiromichi Sugiyama, Jun Hokamaki, Kenichi Komori, Yoshimi Kinoshita, Hironori Murakami, Jun Hashiguchi, Yasuhiro Hashiguchi, Koryo Sawai, Atuko Hifumi, Koji Seo, Masamitsu Toihata, Koji Tokube, Hiroshi Ogawa, Fumishi Tomita, Madoka Taguchi, Toshio Tsubokura, Tatsuaki Tsuchiya, Kaoru Tsuda, Ryuichiro Tsurusaki, Kenji Obata, Katumi Watanabe, Raisuke Hayasida, Yutaka Ishibashi, Yoshiaki Osamura, Yoshito Yamanaka, Kazuhiro Sonoda, Taisuke Iwaoka, Hiromitsu Yokota, Motoki Yoshinari, Nanami Abe, Noriaki Ando, Hiroshi Bando, Takeshi Takami, Michiaki Doi, Yoshihiro Fujii, Masahiro Fukuda, Yoshiaki Fukuoka, Masayoshi Hamano, Minoru Takaoka, Hiromi Hasegawa, Ikuo Yabuta, Kenshi Higami, Satomi Higami, Akiko Yasuno, Yuriko Fujinaga, Yoko Onishi, Katsutoshi Yoshimura, Shigetoshi Minami, Takao Nakashima, Hiroaki Horie, Kazuko Horii, Norihiko Matsumura, Tetsuo Ikuno, Yoshiyuki Katsuyama, Shiro Uemura, Masao Kikukawa, Masao Kanauchi, Hideshi Kuzuya, Arata Iwasaki, Takehiko Koutani, Hisaharu Makino, Hiroshi Miki, Susumu Misugi, Masaki Naito, Masatoshi Naito, Yukitaka Nakano, Akira Nakatani, Fumihiko Nakatani, Manabu Horii, Matahiro Yabuta, Ayako Seno, Hiroyuki Kawata, Kenichi Samejima, Kenji Onoue, Rika Kawakami, Tomoya Nakano, Tomoya Ueda, Tsunenari Soeda, Yoko Kita, Fumitaka Inoue, Shigeru Yamano, Hajime Iwama, Hirokazu Sakan, Megumi Suzuki, Tadashi Kagoshima, Takehito Nakai, Toshio Hashimoto, Yoshiharu Nishitani, Yoshiyuki Kobayashi, Koichi Hoda, Junko Uejima, Yoshinobu Morikawa, Takahiro Kawano, Hideki Yamada, Kazuo Nishimoto, Kyouyuki Ohsumi, Nobushige Ote, Akiko Oya, Kimiaki Nishiura, Joji Masuda, Keiichiro Ban, Yusuke Kyoda, Izumi Sawada, Yoko Sawada, Koichi Okada, Akihiro Yazaki, Masakazu Hanatani, Toshio Sutani, Yuko Hiramori, Yuya Tanaka, Toshiro Igaki, Yukio Tomioka, Hideo Shiiki, Kiyotaka Sugihara, Motomu Hayashi, Yasunobu Sasaki, Yasuo Matsukura, Michiaki Ueda, Masakuni Ueyama, Hideto Uyama, Hiroharu Yamada, Kenichi Yamaga, Tamio Nakajima, Kazumi Yoshimoto, Midori Yoshimura

Funding

This study was supported by the Ministry of Health, Labour and Welfare of Japan (H16-Junkanki-004, and H27-Junkanki-Ippan-001). The study funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Hirofumi Soejima

  2. Health Care Center, Kumamoto University, Kumamoto, Japan

    Hirofumi Soejima

  3. Kumamoto University, Kumamoto, Japan

    Hisao Ogawa

  4. Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan

    Takeshi Morimoto

  5. Department of Diabetes and Endocrinology, Nara Medical University, Kashihara, Japan

    Sadanori Okada

  6. Department of Cardiology, Center for Health Surveillance & Preventive Medicine, Tokyo Medical University Hospital, Tokyo, Japan

    Chisa Matsumoto

  7. Nakayama Cardiovascular Clinic, Amakusa, Japan

    Masafumi Nakayama

  8. Internal Medicine, Koseikai Clinic, Kyoto, Japan

    Izuru Masuda

  9. Department of Internal Medicine, Jinnouchi Hospital Diabetes Care Center, Kumamoto, Japan

    Hideaki Jinnouchi

  10. Food Safety Commission of Japan, Tokyo, Japan

    Masako Waki

  11. Nara Prefecture Seiwa Medical Center, Sango-cho, Japan

    Yoshihiko Saito

Authors
  1. Hirofumi Soejima
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  2. Hisao Ogawa
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  3. Takeshi Morimoto
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  4. Sadanori Okada
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  5. Chisa Matsumoto
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  6. Masafumi Nakayama
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  7. Izuru Masuda
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  8. Hideaki Jinnouchi
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  9. Masako Waki
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  10. Yoshihiko Saito
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Consortia

for the JPAD Trial Investigators

  • Kimiaki Miwa
  • , Kazunobu Akahoshi
  • , Kenji Misumi
  • , Haruo Araki
  • , Yutaka Mitsudo
  • , Norifumi Kondo
  • , Kenichi Ashihara
  • , Shinya Yumoto
  • , Masashi Horimoto
  • , Osamu Doi
  • , Kenichi Doijiri
  • , Ryo Fukami
  • , Michio Shimabukuro
  • , Genshi Egusa
  • , Kazuo Goto
  • , Yoichi Hanaoka
  • , Yoshihiro Kimura
  • , Yoshikuni Haraguchi
  • , Osamu Haraguchi
  • , Atsushi Hasegawa
  • , Yoshiko Shioya
  • , Yosuke Shioya
  • , Eiitiro Tanaka
  • , Kazuhiko Yamada
  • , Toshiya Atsumi
  • , Satoshi Tanazawa
  • , Yutaka Horio
  • , Seishi Ichihara
  • , Isao Yasuda
  • , Tsuneo Ikeda
  • , Makoto Ikemura
  • , Chieko Imamoto
  • , Yoshihisa Iseri
  • , Ken Iwai
  • , Shinya Okamoto
  • , Seigo Sugiyama
  • , Masanori Kamura
  • , Hirofumi Kan
  • , Mayumi Kiyota
  • , Kyousuke Kawamura
  • , Takashi Ono
  • , Takeshi Koga
  • , Etsuo Kinuwaki
  • , Hiromichi Naito
  • , Kazuo Kozuma
  • , Kiyotaka Kudou
  • , Yasuhiro Morikami
  • , Hirofumi Yasue
  • , Yuji Mizuno
  • , Hisao Fujimoto
  • , Kozaburo Matsuyama
  • , Hiromi Fujii
  • , Syuichi Kamijikkoku
  • , Tetsuo Kuwahara
  • , Kyoji Takaoka
  • , Kazuo Machii
  • , Kazutaka Maeda
  • , Keiji Mahara
  • , Akira Maki
  • , Naoki Manda
  • , Kousuke Marutsuka
  • , Naoki Sameshima
  • , Toshihiro Gi
  • , Terufumi Matsunaga
  • , Syuichi Matsuo
  • , Hiroto Okubo
  • , Fuyuki Minagawa
  • , Kotaro Minoda
  • , Junichi Miyata
  • , Takeshi Matsuo
  • , Sueo Momosaki
  • , Tetsuo Munakata
  • , Tomoki Nakamura
  • , Hisatoshi Nagano
  • , Kazuto Goshi
  • , Keisuke Sugimoto
  • , Shojiro Naomi
  • , Toshiaki Nasu
  • , Hiroyuki Tanaka
  • , Ryuji Sonoda
  • , Keizo Kajiwara
  • , Takafumi Odo
  • , Hirofumi Ogata
  • , Masayuki Ogihara
  • , Tateo Ogura
  • , Keishiro Oka
  • , Eiji Kawashima
  • , Eiji Oshima
  • , Ken Ozaki
  • , Seiji Ozawa
  • , Hiroyuki Shono
  • , Yasuhiro Sakamoto
  • , Nobuko Sakurai
  • , Chikashi Wakabayashi
  • , Tomohiro Sawada
  • , Junji Shibata
  • , Hisashi Shimono
  • , Akihiro Iemura
  • , Akira Matsutani
  • , Hisakazu Suefuji
  • , Hiromichi Sugiyama
  • , Jun Hokamaki
  • , Kenichi Komori
  • , Yoshimi Kinoshita
  • , Hironori Murakami
  • , Jun Hashiguchi
  • , Yasuhiro Hashiguchi
  • , Koryo Sawai
  • , Atuko Hifumi
  • , Koji Seo
  • , Masamitsu Toihata
  • , Koji Tokube
  • , Hiroshi Ogawa
  • , Fumishi Tomita
  • , Madoka Taguchi
  • , Toshio Tsubokura
  • , Tatsuaki Tsuchiya
  • , Kaoru Tsuda
  • , Ryuichiro Tsurusaki
  • , Kenji Obata
  • , Katumi Watanabe
  • , Raisuke Hayasida
  • , Yutaka Ishibashi
  • , Yoshiaki Osamura
  • , Yoshito Yamanaka
  • , Kazuhiro Sonoda
  • , Taisuke Iwaoka
  • , Hiromitsu Yokota
  • , Motoki Yoshinari
  • , Nanami Abe
  • , Noriaki Ando
  • , Hiroshi Bando
  • , Takeshi Takami
  • , Michiaki Doi
  • , Yoshihiro Fujii
  • , Masahiro Fukuda
  • , Yoshiaki Fukuoka
  • , Masayoshi Hamano
  • , Minoru Takaoka
  • , Hiromi Hasegawa
  • , Ikuo Yabuta
  • , Kenshi Higami
  • , Satomi Higami
  • , Akiko Yasuno
  • , Yuriko Fujinaga
  • , Yoko Onishi
  • , Katsutoshi Yoshimura
  • , Shigetoshi Minami
  • , Takao Nakashima
  • , Hiroaki Horie
  • , Kazuko Horii
  • , Norihiko Matsumura
  • , Tetsuo Ikuno
  • , Yoshiyuki Katsuyama
  • , Shiro Uemura
  • , Masao Kikukawa
  • , Masao Kanauchi
  • , Hideshi Kuzuya
  • , Arata Iwasaki
  • , Takehiko Koutani
  • , Hisaharu Makino
  • , Hiroshi Miki
  • , Susumu Misugi
  • , Masaki Naito
  • , Masatoshi Naito
  • , Yukitaka Nakano
  • , Akira Nakatani
  • , Fumihiko Nakatani
  • , Manabu Horii
  • , Matahiro Yabuta
  • , Ayako Seno
  • , Hiroyuki Kawata
  • , Kenichi Samejima
  • , Kenji Onoue
  • , Rika Kawakami
  • , Tomoya Nakano
  • , Tomoya Ueda
  • , Tsunenari Soeda
  • , Yoko Kita
  • , Fumitaka Inoue
  • , Shigeru Yamano
  • , Hajime Iwama
  • , Hirokazu Sakan
  • , Megumi Suzuki
  • , Tadashi Kagoshima
  • , Takehito Nakai
  • , Toshio Hashimoto
  • , Yoshiharu Nishitani
  • , Yoshiyuki Kobayashi
  • , Koichi Hoda
  • , Junko Uejima
  • , Yoshinobu Morikawa
  • , Takahiro Kawano
  • , Hideki Yamada
  • , Kazuo Nishimoto
  • , Kyouyuki Ohsumi
  • , Nobushige Ote
  • , Akiko Oya
  • , Kimiaki Nishiura
  • , Joji Masuda
  • , Keiichiro Ban
  • , Yusuke Kyoda
  • , Izumi Sawada
  • , Yoko Sawada
  • , Koichi Okada
  • , Akihiro Yazaki
  • , Masakazu Hanatani
  • , Toshio Sutani
  • , Yuko Hiramori
  • , Yuya Tanaka
  • , Toshiro Igaki
  • , Yukio Tomioka
  • , Hideo Shiiki
  • , Kiyotaka Sugihara
  • , Motomu Hayashi
  • , Yasunobu Sasaki
  • , Yasuo Matsukura
  • , Michiaki Ueda
  • , Masakuni Ueyama
  • , Hideto Uyama
  • , Hiroharu Yamada
  • , Kenichi Yamaga
  • , Tamio Nakajima
  • , Kazumi Yoshimoto
  •  & Midori Yoshimura

Contributions

All authors contributed to the study conception and design. Data collection was performed by HS and SO. Data analysis were performed by TM. The first draft of the manuscript was written by HS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hirofumi Soejima.

Ethics declarations

Conflict of interest

Dr Soejima reports lecturer's fees from Kowa. Dr Ogawa reports lecturer's fees from Bayer, Bristol-Myers Squibb, and Towa; manuscript fee from Novartis. Dr Morimoto reports lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Sanofi. Dr Okada reports lecturer's fees from AstraZeneca, Eli Lilly, Mitsubishi Tanabe, Novartis, Ono, Sumitomo Dainippon, and Takeda. Dr Nakayama reports research grants from Bayer; lecturer's fees from Astellas Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Kowa, Nippon Shinyaku, Ono, Otsuka, Pfizer, Sumitomo Dainippon, and Takeda. Dr Masuda reports lecturer's fees from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kowa, Mitsubishi Tanabe, MSD, Ono, Shionogi, and Takeda. Dr Jinnouchi reports research grants from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, MSD, Novo Nordisk, Ono, Pfizer, Sanofi, Sanwa Kagaku Kenkyusho, Shionogi, Taisho Toyama, and Takeda; lecturer's fees from Abbott, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Kyowa Hakko Kirin, Mitsubishi Tanabe, MSD, Novo Nordisk, Sanofi, Sanwa Kagaku Kenkyusho, Taisho Toyama, Takeda, Teijin, and Terumo; manuscript fees from Novo Nordisk and Taisho Toyama. Dr Waki reports research grants from AstraZeneca, Eli Lilly, and Sanofi; lecturer's fees from Abbott, Astellas, Astellas Amgen Bio Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Kowa, Kyowa Hakko Kirin, Mitsubishi Tanabe, MSD, Novartis, Novo Nordisk, Ono, Otsuka, Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon, Taisho Toyama, Takeda, and Teijin. Dr Saito reports research grants from Actelion, Astellas, Astellas Amgen Bio Pharma, Bayer, Cmic, Daiichi Sankyo, EP‐CRSU, Japan Lifeline, Kowa, Mebix, Meditrix, Novartis, Ono, Roche Diagnostics, and Terumo; non-purpose research grants from Astellas, Chugai, Daiichi Sankyo, Fuji Yakuhin, Kowa, Kyowa Hakko Kirin, Medtronic, Mitsubishi Tanabe, MSD, Nihon Medi-Physics, Ono, Otsuka, Sanofi, Shionogi, Sumitomo Dainippon, Takeda, and Teijin; lecturer’s fees from Alnylam, Asahi Kasei, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen, Kowa, Mitsubishi Tanabe, MSD, Novartis, Ono, Otsuka, Pfizer, Taisho Toyama, Takeda, and Toa Eiyo; manuscript fees from Asahi Kasei and Novartis; advisory boards for Amgen, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe, Novartis, Ono, Pfizer, and Roche Diagnostics. The other authors have no conflicts of interest to declare.

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Soejima, H., Ogawa, H., Morimoto, T. et al. Dipeptidyl peptidase-4 inhibitors reduce the incidence of first cardiovascular events in Japanese diabetic patients. Heart Vessels 38, 1371–1379 (2023). https://doi.org/10.1007/s00380-023-02291-4

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