Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Cardiovasc Diabetol. 2020 Jul 9;19(1):110. 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.
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 ).
本研究旨在通过监测颈动脉内膜中层厚度（IMT）来探讨选择性钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂托格列净对无明显心血管疾病（CVD）的 2 型糖尿病（T2DM）患者动脉粥样硬化进展的预防作用。
这是一项前瞻性、随机、开放标签、盲终点、多中心、平行组、对照研究，纳入了 24 个临床单位的 340 名无明显 CVD 病史的 T2DM 患者。患者被随机分配至托格列净治疗组（n=169）或使用除 SGLT2 抑制剂以外的药物的常规治疗组（n=171）。主要结局为在 104 周治疗期间通过超声测量的颈总动脉平均和最大 IMT 的变化。
在混合效应重复测量模型中，颈总动脉平均 IMT（平均 IMT-CCA）以及右侧和左侧颈总动脉最大 IMT（最大 IMT-CCA）在托格列净组（-0.132mm，SE 0.007；-0.163mm，SE 0.013；-0.170mm，SE 0.020）和对照组（-0.140mm，SE 0.006；-0.190mm，SE 0.012；-0.190mm，SE 0.020）均显著下降。此外，托格列净组和常规治疗组在平均 IMT-CCA 的进展方面没有显著差异（平均变化（95%CI）0.008（-0.009，0.025）mm，P=0.34），以及右侧（平均变化（95%CI）0.027（-0.005，0.059）mm，P=0.10）和左侧最大 IMT-CCA（平均变化（95%CI）0.020（-0.030，0.070）mm，P=0.43）。即使在调整了传统的 CV 危险因素和/或基线时的药物治疗后，仍得到了相似的发现。与对照组治疗效果相比，托格列净显著降低了 HbA1c、血糖水平、体重/体重指数、腰围和收缩压，同时显著增加了高密度脂蛋白胆固醇。两组的总不良事件和严重不良事件发生率无显著差异。
结论/解释：托格列净组和常规治疗组之间的 IMT 变化没有观察到差异。然而，托格列净是一种安全有效的治疗方案，可用于管理该人群的主要 CVD 风险因素。临床试验注册号 UMIN000017607（https://www.umin.ac.jp/icdr/index.html）。
