Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective, randomized, open-label, parallel-group comparative study

Cardiovascular Diabetology

the UTOPIA study investigators¹  Kayoko Ryomoto²  Satoru Sumitani³  Yutaka Umayahara⁴  Tetsuyuki Yasuda⁵  Hideaki Kaneto⁶  Mamiko Tsugawa⁷  Tadashi Nakamura⁸  Hidenori Yoshii⁹  Naoto Katakami^1,10  Iichiro Shimomura^1,10  Hirotaka Watada^1,11  Tomoya Mita^1,11  Yasunori Sato^1,12  Hideki Taki^1,13  Tsunehiko Yamamoto^1,14  Yosuke Okada^1,15  Keiichi Torimoto^1,15  Isao Hayashi^1,16  Hiroki Yokoyama^1,17  Satoshi Kawashima^1,18  Kazuhisa Maeda^1,19  Keisuke Kosugi^2,20  Nobuichi Kuribayashi^2,21  Takeshi Osonoi^2,22  Kentaro Ohtoshi^2,23  Toshihiko Shiraiwa^2,24 

[1] ;Center for Diabetes Mellitus, Osaka Rosai Hospital;Center for Diabetes and Endocrinology, Nippon Life Hospital;Department of Diabetes and Endocrinology, Osaka General Medical Center;Department of Diabetes and Endocrinology, Osaka Police Hospital;Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School;Department of Endocrinology and Metabolism, Ikeda Municipal Hospital;Department of Internal Medicine, Kawasaki Hospital;Department of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center;Department of Metabolic Medicine, Osaka University Graduate School of Medicine;Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine;Department of Preventive Medicine and Public Health, Keio University School of Medicine;Diabetes Center, National Hospital Organization Osaka National Hospital;Diabetes and Endocrinology, Kansai Rosai Hospital;First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan;Hayashi Clinic;Jiyugaoka Medical Clinic;Kanda Naika Clinic;Kitasenri Maeda Clinic;Kosugi Medical Clinic;Misaki Naika Clinic;Nakakinen Clinic;Otoshi Medical Clinic;Shiraiwa Medical Clinic;

关键词: Atherosclerosis;    Diabetes;    Intima-media thickness;    SGLT2 inhibitor;    Tofogliflozin;   

DOI  :  10.1186/s12933-020-01079-4

来源: DOAJ

【 摘 要 】

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 ).

【 授权许可】

Unknown