Long-term effects of ipragliflozin on blood pressure in patients with type 2 diabetes: insights from the randomized PROTECT trial
Year: 2023
Type: article
Abstract: Background/Aims 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 patients with type 2 diabetes. Methods This was a sub-analysis of the PROTECT (Prevention of atherosclerosis by SGLT2 inhibitor: multicenter, randomized controlled study) trial, a multicenter, randomized, open-label, blinded-endpoint study to assess if ipragliflozin delays carotid intima-media thickness progression 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, which was measured in a routine clinical setting at baseline and at 3, 6, 12 and 24 months. Correlations between systolic BP changes and cardiometabolic variables during the follow-up period were also evaluated. Results A total of 232 patients with well-balanced baseline characteristics were included in each study group. During the 24-month follow-up, systolic BP was consistently lower in the ipragliflozin group than the control group. Throughout the 24-month observation period, mean systolic BP was lower in the ipragliflozin group by 3.6 mm Hg (95% confidence interval, 0.7 to 6.5 mm Hg) across several subgroups. Changes in systolic BP correlated significantly with changes in body mass index particularly in the ipragliflozin group, while no significant correlations between changes in systolic BP and carotid intima-media thickness, estimated glomerular filtration rate, or N-terminal pro-B-type natriuretic peptide were observed from baseline to 24 months. Conclusions 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 a major mechanism for the BP lowering effect of SGLT2 inhibitors. Trial registration University Hospital Medical Information Network Clinical Trial Registry; UMIN000018440 and Japan Registry of Clinical Trials; jRCTs071180041 and jRCT1071220089.
Source: Hypertension Research
Authors: Yuichi Saito, Atsushi Tanaka, Takumi Imai, Ikuko Nakamura, Junji Kanda, Munehide Matsuhisa, Hiroki Uehara, Kazuomi Kario, Yoshio Kobayashi, Koichi Node, on behalf of the PROTECT investigators, Principal Investigators, Koichi Node, Toyoaki Murohara, Masafumi Kitakaze, Yoshihiko Nishio, Teruo Inoue, Mitsuru Ohishi, Kazuomi Kario, Masataka Sata, Michio Shimabukuro, Wataru Shimizu, Hideaki Jinnouchi, Isao Taguchi, Hirofumi Tomiyama, Koji Maemura, 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, Tomoko Ishizu, Monitoring, Yumi Ikehara, Shinichiro Ueda, Audit Team, 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, 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
Institutions: Chiba University, Saga University, Kobe University Hospital, Saga-Ken Medical Centre Koseikan, Asahi General Hospital, Diabetes Therapeutics and Research Center, Tokushima University, Tokushima University, Urasoe General Hospital, Jichi Medical University, Nagoya University, Gunma Saiseikai Maebashi Hospital, Kagoshima University, Dokkyo Medical University, Fukushima Medical University, Nippon Medical School, Dokkyo Medical University Saitama Medical Center, Tokyo Medical University, Nagasaki University, Yokohama Minami Kyosai Hospital, Saitama Red Cross Hospital, Japanese Red Cross Nagoya Daiichi Hospital, Saiseikai Kumamoto Hospital, Kitasato University, Hyogo Medical University, Tokyo Women's Medical University, Kiryu University, University of Tsukuba, University of the Ryukyus University Hospital, Osaka Metropolitan University, Hiroshima University, Miyazaki Medical Association Hospital, International University of Health and Welfare, National Defense Medical College, Japanese Red Cross Nagoya Daini Hospital, Imari Arita Kyoritsu Hospital, Osaka Medical and Pharmaceutical University, Tosei General Hospital, Kasugai Municipal Hospital, Fukuoka University, Nagoya City University, Osaka City University, University of Occupational and Environmental Health Japan, Wakayama Medical University, Aidu Chuo Hospital, Ohta Nishinouchi Hospital, Wakamatsu Hospital of the University of Occupational and Environmental Health, Japan
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Bristol-Myers Squibb, Eli Lilly and Company, AstraZeneca, GlaxoSmithKline, Abbott Japan, Kowa Company, Boehringer Ingelheim Japan, JCR Pharmaceuticals, Daiichi-Sankyo, Novo Nordisk, Astellas Pharma, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical, Novartis Pharma, Eli Lilly Japan, Bayer Yakuhin, Novo Nordisk Pharma, Japan Society for the Promotion of Science, Daiichi Sankyo Europe
OpenAlex ID: W4388658043