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. 2023 Jun 22;22(1):143. doi: 10.1186/s12933-023-01879-4.
This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease.
This was a prospective observational 2-year extension study of the "Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)" trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks.
The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (- 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (- 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) - 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (- 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (- 100.2 cm/s, 95% CI - 182.8 to - 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups.
Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile.
本研究旨在评估钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂托格列净在无明显心血管疾病史的 2 型糖尿病患者中的长期疗效，评估其对动脉粥样硬化进展和主要临床参数的影响。
这是一项为期 2 年的“使用托格列净治疗 2 型糖尿病患者以可能更好地干预动脉粥样硬化（UTOPIA）”试验的前瞻性观察性 2 年扩展研究，该试验为一项为期 2 年的随机干预研究。主要终点是颈动脉内膜中层厚度（IMT）的变化。次要终点包括臂踝脉搏波速度（baPWV）和葡萄糖代谢、脂质代谢、肾功能和心血管风险的生物标志物。
在整个随访期间，颈动脉（CCA-IMT）的平均 IMT 在托格列净组（-0.067mm，标准误差 0.009，p<0.001）和常规治疗组（-0.080mm，SE 0.009，p<0.001）均显著降低；然而，在混合效应重复测量模型中，两组间的变化无显著差异（0.013mm，95%置信区间（CI）-0.012 至 0.037，p=0.32）。baPWV 在常规治疗组显著增加（82.7±210.3cm/s，p=0.008），而在托格列净组无显著增加（-17.5±221.3cm/s，p=0.54），两组间的变化存在显著差异（-100.2cm/s，95%CI-182.8 至-17.5，p=0.018）。与常规治疗组相比，托格列净显著改善了血红蛋白 A1c 和高密度脂蛋白胆固醇水平、体重指数、腰围和收缩压。两组的总不良事件和严重不良事件发生率无显著差异。
托格列净与改善颈动脉壁增厚的抑制作用无关，但长期对各种心血管危险因素和 baPWV 有积极影响，同时具有良好的安全性。
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