Effect of ipragliflozin on carotid intima-media thickness in patients with type 2 diabetes: a multicenter, randomized, controlled trial
Authors: Tanaka Atsushi , Sata Masataka , Okada Yosuke , Teragawa Hiroki , Eguchi Kazuo , Shimabukuro Michio , Taguchi Isao , Matsunaga Kazuo , Kanzaki Yumiko , Yoshida Hisako , Ishizu Tomoko , Ueda Shinichiro , Kitakaze Masafumi , Murohara Toyoaki , Node Koichi ,   the PROTECT study investigators, Node Koichi , Murohara Toyoaki , Kitakaze Masafumi , Nishio Yoshihiko , Inoue Teruo , Ohishi Mitsuru , Kario Kazuomi , Sata Masataka , Shimabukuro Michio , Shimizu Wataru , Jinnouchi Hideaki , Taguchi Isao , Tomiyama Hirofumi , Maemura Koji , Suzuki Makoto , Ando Shinichi , Eguchi Kazuo , Kamiya Haruo , Sakamoto Tomohiro , Teragawa Hiroki , Nanasato Mamoru , Matsuhisa Munehide , Ako Junya , Aso Yoshimasa , Ishihara Masaharu , Kitagawa Kazuo , Yamashina Akira , Ishizu Tomoko , Ikehara Yumi , Ueda Shinichiro , Takamori Ayako , Tanaka Atsushi , Mori Miki , Yamaguchi Kaori , Asaka Machiko , Kaneko Tetsuya , Sakuma Masashi , Toyoda Shigeru , Nasuno Takahisa , Kageyama Michiya , Teruo Jojima , Toshie Iijima , Kishi Haruka , Yamada Hirotsugu , Kusunose Kenya , Fukuda Daiju , Yagi Shusuke , Yamaguchi Koji , Ise Takayuki , Kawabata Yutaka , Kuroda Akio , Akasaki Yuichi , Kurano Mihoko , Hoshide Satoshi , Komori Takahiro , Kabutoya Tomoyuki , Ogata Yukiyo , Koide Yuji , Kawano Hiroaki , Ikeda Satoshi , Fukae Satoki , Koga Seiji , Higashi Yukihito , Kishimoto Shinji , Kajikawa Masato , Maruhashi Tatsuya , Kubota Yoshiaki , Shibata Yoshisato , Kuriyama Nehiro , Nakamura Ikuko , Hironori Kanemitsu , Takase Bonpei , Orita Yuichi , Oshita Chikage , Uchimura Yuko , Yoshida Ruka , Yoshida Yukihiko , Suzuki Hirohiko , Ogura Yasuhiro , Maeda Mayuho , Takenaka Masaki , Hayashi Takumi , Hirose Mirai , Hisauchi Itaru , Kadokami Toshiaki , Nakamura Ryo , Kanda Junji , Matsunaga Kazuo , Hoshiga Masaaki , Sohmiya Koichi , Kanzaki Yumiko , Koyosue Arihiro , Uehara Hiroki , Miyagi Naoto , Chinen Toshiya , Nakamura Kentaro , Nago Chikashi , Chiba Suguru , Hatano Sho , Gima Yoshikatsu , Abe Masami , Ajioka Masayoshi , Asano Hiroshi , Nakashima Yoshihiro , Osanai Hiroyuki , Kanbara Takahiro , Sakamoto Yusuke , Oguri Mitsutoshi , Ohguchi Shiou , Takahara Kunihiko , Izumi Kazuhiro , Yasuda Kenichiro , Kudo Akihiro , Machii Noritaka , Morimoto Ryota , Bando Yasuko , Okumura Takahiro , Kondo Toru , Miura Shin-ichiro , Shiga Yuhei , Mirii Joji , Sugihara Makoto , Arimura Tadaaki , Nakano Junko , Sakamoto Tomohiro , Kodama Kazuhisa , Ohte Nobuyuki , Sugiura Tomonori , Wakami Kazuaki , Takemoto Yasuhiko , Yoshiyama Minoru , Shuto Taichi , Fukumoto Kazuo , Okada Yosuke , Tanaka Kenichi , Sonoda Satomi , Tokutsu Akemi , Otsuka Takashi , Uemura Fumi , Koikawa Kenji , Miyazaki Megumi , Umikawa Maiko , Narisawa Manabu , Furuta Machi , Minami Hiroshi , Doi Masaru , Sugimoto Kazuhiro , Suzuki Susumu , Kurozumi Akira , Nishio Kosuke 
Published: October 2022

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.