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

• Published in: Cardiovascular diabetology Vol. 19; no. 1; pp. 110 - 16
• Main Authors: Katakami, Naoto, Mita, Tomoya, Yoshii, Hidenori, Shiraiwa, Toshihiko, Yasuda, Tetsuyuki, Okada, Yosuke, Torimoto, Keiichi, Umayahara, Yutaka, Kaneto, Hideaki, Osonoi, Takeshi, Yamamoto, Tsunehiko, Kuribayashi, Nobuichi, Maeda, Kazuhisa, Yokoyama, Hiroki, Kosugi, Keisuke, Ohtoshi, Kentaro, Hayashi, Isao, Sumitani, Satoru, Tsugawa, Mamiko, Ryomoto, Kayoko, Taki, Hideki, Nakamura, Tadashi, Kawashima, Satoshi, Sato, Yasunori, Watada, Hirotaka, Shimomura, Iichiro
• Format: Journal Article
• Language: English
• Published: England BioMed Central 09.07.2020; BMC
• Subjects: Aged; Antihypertensives; Arteriosclerosis; Atherosclerosis; Benzhydryl Compounds - adverse effects; Benzhydryl Compounds - therapeutic use; Blood pressure; Body mass index; Body weight; Cardiovascular diseases; Carotid arteries; Carotid artery; Carotid Artery Diseases - diagnostic imaging; Carotid Artery Diseases - epidemiology; Carotid Artery Diseases - prevention & control; Carotid Intima-Media Thickness; Clinical trials; Consent; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Disease Progression; Drug dosages; Female; Glucose; Glucosides - adverse effects; Glucosides - therapeutic use; Heart attacks; Heart failure; High density lipoprotein; Humans; Hypoglycemia; Intima-media thickness; Japan - epidemiology; Male; Middle Aged; Na+/glucose cotransporter; Original Investigation; Patients; Physical therapy; Prospective Studies; Registration; Risk factors; SGLT2 inhibitor; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Software; Stroke; Time Factors; Tofogliflozin; Treatment Outcome; Veins & arteries; Japan; Tofogliflozin; Intima-media thickness; Diabetes; SGLT2 inhibitor; Atherosclerosis
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-020-01079-4

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). 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. 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. 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 ).