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 City, 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 City, Ibaraki, 311-0113, Japan. 11. Diabetes and Endocrinology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki City, Hyogo, Japan. 12. Misaki Naika Clinic, 6-44-9, Futawa-higashi, Funabashi City, 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, Kobe Hyogo-ku, 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: This study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT). METHODS: This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period. RESULTS: In a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (- 0.132 mm, SE 0.007; - 0.163 mm, SE 0.013; - 0.170 mm, SE 0.020, respectively) and the control group (- 0.140 mm, SE 0.006; - 0.190 mm, SE 0.012; - 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (- 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (- 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (- 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups. CONCLUSIONS/ INTERPRETATION: No IMT changes were observed between the tofogliflozin and the conventional treatment groups. However, tofogliflozin is a safe and effective treatment option for managing primary CVD risk factors in this population. Clinical Trial Registration UMIN000017607 ( https://www.umin.ac.jp/icdr/index.html ).
RCT Entities:
BACKGROUND: This study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT). METHODS: This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period. RESULTS: In a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (- 0.132 mm, SE 0.007; - 0.163 mm, SE 0.013; - 0.170 mm, SE 0.020, respectively) and the control group (- 0.140 mm, SE 0.006; - 0.190 mm, SE 0.012; - 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (- 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (- 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (- 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups. CONCLUSIONS/ INTERPRETATION: No IMT changes were observed between the tofogliflozin and the conventional treatment groups. However, tofogliflozin is a safe and effective treatment option for managing primary CVD risk factors in this population. Clinical Trial Registration UMIN000017607 ( https://www.umin.ac.jp/icdr/index.html ).
Authors: Judit Hodrea; Adar Saeed; Agnes Molnar; Attila Fintha; Adrienn Barczi; Laszlo J Wagner; Attila J Szabo; Andrea Fekete; Dora B Balogh Journal: PLoS One Date: 2022-02-17 Impact factor: 3.240
Authors: Thahesh Tharmaraja; Jamie S Y Ho; Ching-Hui Sia; Nicole-Ann Lim; Yao Feng Chong; Amanda Y L Lim; Rahul R Rathakrishnan; Leonard L L Yeo; Vijay K Sharma; Benjamin Y Q Tan Journal: Ther Adv Chronic Dis Date: 2022-04-11 Impact factor: 5.091