Effect of ipragliflozin on carotid intima-media thickness in patients with type 2 diabetes: a multicenter, randomized, controlled trial
Atsushi Tanaka, Masataka Sata, Yosuke Okada, Hiroki Teragawa, Kazuo Eguchi, Michio Shimabukuro, Isao Taguchi, Kazuo Matsunaga, Yumiko Kanzaki, Hisako Yoshida, Tomoko Ishizu, Shinichiro Ueda, Masafumi Kitakaze, Toyoaki Murohara, Koichi Node, the PROTECT study 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, Shin‐ichi Ando, Kazuo Eguchi, Haruo Kamiya, Tomohiro Sakamoto, Hiroki Teragawa, Mamoru Nanasato, Munehide Matsuhisa, Junya Ako, Yoshimasa Aso, Masaharu Ishihara, Kazuo Kitagawa, Akira Yamashina, Tomoko Ishizu, Yumi Ikehara, Shinichiro Ueda, Ayako Takamori, Atsushi Tanaka, Miki Mori, Kaori Yamaguchi, Machiko Asaka, Tetsuya Kaneko, Masashi Sakuma, Shigeru Toyoda, Takahisa Nasuno, Michiya Kageyama, Jojima Teruo, Toshie Iijima, 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
Abstract
AIMS: To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. METHODS AND RESULTS: In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0-10.0% (42-86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), -0.0155-0.0182] mm and 0.0015 (95% CI, -0.0155-0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of -0.0001 mm (95% CI, -0.0191-0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [-0.1% (95% CI, -0.2-0.1); P = 0.359]. CONCLUSION: Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.