Naoto Katakami1,2, Tomoya Mita3, Hidenori Yoshii4, Toshihiko Shiraiwa5, Tetsuyuki Yasuda6, Yosuke Okada7, Keiichi Torimoto7, Yutaka Umayahara8, Hideaki Kaneto9, Takeshi Osonoi10, Tsunehiko Yamamoto11, Nobuichi Kuribayashi12, Kazuhisa Maeda13, Hiroki Yokoyama14, Keisuke Kosugi15, Kentaro Ohtoshi16, Isao Hayashi17, Satoru Sumitani18, Mamiko Tsugawa19, Kayoko Ryomoto20, Hideki Taki21, Tadashi Nakamura22, Satoshi Kawashima23, Yasunori Sato24, Hirotaka Watada3, Iichiro Shimomura25. 1. Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan. katakami@endmet.med.osaka-u.ac.jp. 2. Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan. katakami@endmet.med.osaka-u.ac.jp. 3. Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan. 4. Department of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Koto-ku, Tokyo, 136-0075, Japan. 5. Shiraiwa Medical Clinic, 4-10-24 Hozenji, Kashiwara, Osaka, 582-0005, Japan. 6. Department of Diabetes and Endocrinology, Osaka Police Hospital, 10-31, Kitayama-cho, Tennoji-ku, Osaka, 543-0035, Japan. 7. First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. 8. Department of Diabetes and Endocrinology, Osaka General Medical Center, 3-1-56, Bandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan. 9. Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan. 10. Nakakinen Clinic, 745-5, Nakadai, Naka, Ibaraki, 311-0113, Japan. 11. Diabetes and Endocrinology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, Japan. 12. Misaki Naika Clinic, 6-44-9, Futawa-higashi, Funabashi, Chiba, Japan. 13. Kitasenri Maeda Clinic, 4-119, Furuedai, Suita, Osaka, 565-0874, Japan. 14. Jiyugaoka Medical Clinic, West 6, South 6-4-3, Obihiro, Hokkaido, 080-0016, Japan. 15. Kosugi Medical Clinic, 3-9, Tamatsukurimoto-cho, Tennoji-ku, Osaka, 543-0014, Japan. 16. Otoshi Medical Clinic, 8-47, Kakudacho, Osaka Kita-ku, Osaka, 530-0017, Japan. 17. Hayashi Clinic, 3-9-23, Koshienguchi, Nishinomiya, Hyogo, 663-8113, Japan. 18. Center for Diabetes and Endocrinology, Nippon Life Hospital, 2-1-54 Enokojima, Nishi-ku, Osaka, 550-0006, Japan. 19. Department of Endocrinology and Metabolism, Ikeda Municipal Hospital, 3-1-18, Jonan, Ikeda, Osaka, 563-8510, Japan. 20. Center for Diabetes Mellitus, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Kita-ku, Sakai, Osaka, 591-8025, Japan. 21. Diabetes Center, National Hospital Organization Osaka National Hospital, 2-1-14, Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan. 22. Department of Internal Medicine, Kawasaki Hospital, 3-3-1, Higashiyamacho, Hyogo-ku, Kobe, Hyogo, 652-0042, Japan. 23. Kanda Naika Clinic, 5-21-3, Hannancho, Osaka Abeno-ku, Osaka, 545-0021, Japan. 24. Department of Preventive Medicine and Public Health, Keio University School of Medicine, 45 Shinanomachi Shinjuku-ku, Tokyo, 160-8582, Japan. 25. Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Abstract
BACKGROUND:Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease. METHODS: The using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in thetofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline. RESULTS: In a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (- 109.3 [- 184.3, - 34.3] (mean change [95% CI] cm/s, p = 0.005; - 98.3 [- 172.6, - 24.1] cm/s, p = 0.010; - 104.7 [- 177.0, - 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models. CONCLUSIONS:Tofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness. Trial Registration UMIN000017607. Registered 18 May 2015. ( https://www.umin.ac.jp/icdr/index.html ).
RCT Entities:
BACKGROUND:Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease. METHODS: The using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetespatients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline. RESULTS: In a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (- 109.3 [- 184.3, - 34.3] (mean change [95% CI] cm/s, p = 0.005; - 98.3 [- 172.6, - 24.1] cm/s, p = 0.010; - 104.7 [- 177.0, - 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models. CONCLUSIONS:Tofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness. Trial Registration UMIN000017607. Registered 18 May 2015. ( https://www.umin.ac.jp/icdr/index.html ).
Authors: N Takashima; T C Turin; K Matsui; N Rumana; Y Nakamura; A Kadota; Y Saito; H Sugihara; Y Morita; M Ichikawa; K Hirose; K Kawakani; N Hamajima; K Miura; H Ueshima; Y Kita Journal: J Hum Hypertens Date: 2013-10-31 Impact factor: 3.012
Authors: Stephen D Wiviott; Itamar Raz; Marc P Bonaca; Ofri Mosenzon; Eri T Kato; Avivit Cahn; Michael G Silverman; Thomas A Zelniker; Julia F Kuder; Sabina A Murphy; Deepak L Bhatt; Lawrence A Leiter; Darren K McGuire; John P H Wilding; Christian T Ruff; Ingrid A M Gause-Nilsson; Martin Fredriksson; Peter A Johansson; Anna-Maria Langkilde; Marc S Sabatine Journal: N Engl J Med Date: 2018-11-10 Impact factor: 91.245
Authors: Bruce Neal; Vlado Perkovic; Kenneth W Mahaffey; Dick de Zeeuw; Greg Fulcher; Ngozi Erondu; Wayne Shaw; Gordon Law; Mehul Desai; David R Matthews Journal: N Engl J Med Date: 2017-06-12 Impact factor: 91.245
Authors: Michael Pfeifer; Raymond R Townsend; Michael J Davies; Ujjwala Vijapurkar; Jimmy Ren Journal: Cardiovasc Diabetol Date: 2017-02-27 Impact factor: 9.951
Authors: David Zi Cherney; Bruce A Perkins; Nima Soleymanlou; Ronnie Har; Nora Fagan; Odd Erik Johansen; Hans-Juergen Woerle; Maximilian von Eynatten; Uli C Broedl Journal: Cardiovasc Diabetol Date: 2014-01-29 Impact factor: 9.951