Cardiovascular Diabetology (Jul 2020)

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

  • Naoto Katakami,
  • Tomoya Mita,
  • Hidenori Yoshii,
  • Toshihiko Shiraiwa,
  • Tetsuyuki Yasuda,
  • Yosuke Okada,
  • Keiichi Torimoto,
  • Yutaka Umayahara,
  • Hideaki Kaneto,
  • Takeshi Osonoi,
  • Tsunehiko Yamamoto,
  • Nobuichi Kuribayashi,
  • Kazuhisa Maeda,
  • Hiroki Yokoyama,
  • Keisuke Kosugi,
  • Kentaro Ohtoshi,
  • Isao Hayashi,
  • Satoru Sumitani,
  • Mamiko Tsugawa,
  • Kayoko Ryomoto,
  • Hideki Taki,
  • Tadashi Nakamura,
  • Satoshi Kawashima,
  • Yasunori Sato,
  • Hirotaka Watada,
  • Iichiro Shimomura,
  • the UTOPIA study investigators

DOI
https://doi.org/10.1186/s12933-020-01079-4
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 16

Abstract

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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 ).

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