胰高血糖素样肽-1类似物利拉鲁肽与甘精胰岛素对内皮功能和代谢参数影响的比较：一项随机对照试验——札幌动脉粥样硬化肠促胰岛素研究2（SAIS2）
A Comparison of the Effects of the GLP-1 Analogue Liraglutide and Insulin Glargine on Endothelial Function and Metabolic Parameters: A Randomized, Controlled Trial Sapporo Athero-Incretin Study 2 (SAIS2).
作者信息
Nomoto Hiroshi, Miyoshi Hideaki, Furumoto Tomoo, Oba Koji, Tsutsui Hiroyuki, Miyoshi Arina, Kondo Takuma, Tsuchida Kenichi, Atsumi Tatsuya, Manda Naoki, Kurihara Yoshio, Aoki Shin
机构信息
Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Department of Cardiovascular Medicine, NTT East Japan Sapporo Hospital, Sapporo, Japan; Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
出版信息
PLoS One. 2015 Aug 18;10(8):e0135854. doi: 10.1371/journal.pone.0135854. eCollection 2015.
OBJECTIVES
GLP-1 improves hyperglycemia, and it has been reported to have favorable effects on atherosclerosis. However, it has not been fully elucidated whether GLP-1 is able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of the GLP-1 analogue, liraglutide on endothelial function and glycemic metabolism compared with insulin glargine therapy.
MATERIALS AND METHODS
In this multicenter, prospective randomized parallel-group comparison study, 31 diabetic outpatients (aged 60.3 ± 10.3 years with HbA1c levels of 8.6 ± 0.8%) with current metformin and/or sulfonylurea treatment were enrolled and randomly assigned to receive liraglutide or glargine therapy once daily for 14 weeks. Flow mediated dilation (FMD), a comprehensive panel of hemodynamic parameters (Task Force Monitor), and serum metabolic markers were assessed before and after the treatment period.
RESULTS
A greater reduction (worsening) in %FMD was observed in the glargine group, although this change was not statistically different from the liraglutide group (liraglutide; 5.7 to 5.4%, glargine 6.7 to 5.7%). The augmentation index, C-peptide index, derivatives of reactive oxygen metabolites and BMI were significantly improved in the liraglutide group. Central systolic blood pressure and NT-proBNP also tended to be improved in the liraglutide-treated group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different.
CONCLUSIONS
Regardless of glycemic improvement, early liraglutide therapy did not affect endothelial function but may provide favorable effects on beta-cell function and cardioprotection in type 2 diabetics without advanced atherosclerosis.
TRIAL REGISTRATION
UMIN Clinical Trials Registry System as trial ID UMIN000005331.
目的
胰高血糖素样肽-1（GLP-1）可改善高血糖，且据报道对动脉粥样硬化有有益作用。然而，GLP-1是否能够改善2型糖尿病患者的内皮功能尚未完全阐明。因此，我们研究了与甘精胰岛素治疗相比，GLP-1类似物利拉鲁肽对内皮功能和糖代谢的疗效。
材料与方法
在这项多中心、前瞻性随机平行组比较研究中，纳入了31例正在接受二甲双胍和/或磺脲类药物治疗的糖尿病门诊患者（年龄60.3±10.3岁，糖化血红蛋白水平8.6±0.8%），并将其随机分为两组，分别接受每日一次的利拉鲁肽或甘精胰岛素治疗，为期14周。在治疗前后评估血流介导的血管舒张（FMD）、一组全面的血流动力学参数（特鲁夫斯监测仪）以及血清代谢标志物。
结果
甘精胰岛素组的FMD百分比降低（恶化）幅度更大，尽管这一变化与利拉鲁肽组无统计学差异（利拉鲁肽组：从5.7%降至5.4%，甘精胰岛素组：从6.7%降至5.7%）。利拉鲁肽组的增强指数、C肽指数、活性氧代谢产物衍生物和体重指数显著改善。利拉鲁肽治疗组的中心收缩压和N末端脑钠肽前体也有改善趋势，而两组糖化血红蛋白水平的改善情况相似。心指数、血压和大多数其他代谢参数无差异。
结论
无论血糖改善情况如何，早期利拉鲁肽治疗对内皮功能无影响，但可能对无晚期动脉粥样硬化的2型糖尿病患者的β细胞功能和心脏保护有有益作用。
试验注册
UMIN临床试验注册系统，试验编号UMIN000005331。
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