Shigiyama Fumika, Kumashiro Naoki, Miyagi Masahiko, Iga Ryo, Kobayashi Yuka, Kanda Eiichiro, Uchino Hiroshi, Hirose Takahisa
Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
Department of Nephrology, Tokyo Kyosai Hospital, Tokyo, Japan.
J Diabetes Investig. 2017 May;8(3):330-340. doi: 10.1111/jdi.12587. Epub 2016 Nov 21.
AIMS/INTRODUCTION: The present multicenter, prospective, controlled, open and randomized three-arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function.
Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add-on group, n = 29) and treated for 16 weeks. Vascular endothelial function was evaluated by flow-mediated dilation. The primary end-point was changes in flow-mediated dilation at 16 weeks relative to baseline.
Linagliptin significantly improved flow-mediated dilation from baseline (4.9 ± 2.7%) to 16 weeks (6.3 ± 2.7%, P < 0.05), whereas the other groups did not show any changes. Hemoglobin A1c at 16 weeks was significantly lower in the metformin and linagliptin add-on groups compared with the control (6.6 ± 0.6%, 6.5 ± 0.5% and 7.0 ± 0.6%, respectively). Single and multiple regression analyses showed that apolipoprotein B correlated significantly with change in flow-mediated dilation, and apolipoprotein B was decreased only in the linagliptin add-on group (-6.0 ± 11.3 mg/dL, P < 0.01).
Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.
目的/引言：本多中心、前瞻性、对照、开放且随机的三臂平行研究旨在比较利格列汀与二甲双胍对内皮功能的影响。
接受750毫克二甲双胍治疗（糖化血红蛋白≥6.0%且<8.0%，n = 96）的2型糖尿病患者被随机分为继续每日服用750毫克二甲双胍组（对照组，n = 29）、每日服用1500毫克二甲双胍组（二甲双胍组，n = 26）和每日服用750毫克二甲双胍并加用5毫克利格列汀组（利格列汀加用组，n = 29），治疗16周。通过血流介导的血管舒张功能评估血管内皮功能。主要终点是16周时相对于基线血流介导的血管舒张功能的变化。
利格列汀显著改善了从基线（4.9±2.7%）到16周时的血流介导的血管舒张功能（6.3±2.7%，P<0.05），而其他组未显示任何变化。与对照组相比，二甲双胍组和利格列汀加用组在16周时的糖化血红蛋白显著更低（分别为6.6±0.6%、6.5±0.5%和7.0±0.6%）。单因素和多因素回归分析显示，载脂蛋白B与血流介导的血管舒张功能变化显著相关，且仅在利格列汀加用组载脂蛋白B降低（-6.0±11.3毫克/分升，P<0.01）。
利格列汀治疗16周可改善内皮功能并适度改善血糖控制。这种作用至少部分是通过降低载脂蛋白B介导的。利格列汀对中度高血糖的2型糖尿病患者的内皮功能具有保护作用。
