Nishimura Akihiro, Usui Shuki, Kumashiro Naoki, Uchino Hiroshi, Yamato Azusa, Yasuda Daijiro, Nagasawa Kaoru, Okubo Minoru, Mori Yasumichi, Hirose Takahisa
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Endocr J. 2016 Dec 30;63(12):1087-1098. doi: 10.1507/endocrj.EJ16-0291. Epub 2016 Sep 17.
Although sitagliptin and repaglinide monotherapies improve postprandial hyperglycemia, the long-term effects and safety of their combination has not been examined. In this randomized 24-week trial of Japanese patients with poor control (HbA1c 7.0-8.5%) by sitagliptin, we divided 40 patients randomly into two equal groups of the repaglinide add-on to sitagliptin (ADD-ON, n=20), or sitagliptin switched to repaglinide (SWITCH, n=20). The meal tolerance test was carried out at weeks 0 and 24. The primary outcomes were changes in HbA1c and area under the curves (AUC) of glucose from the baseline to week 24. The mean change in HbA1c from baseline to week 24 was larger in the ADD-ON (-0.87±0.63%, mean±SD), compared with the SWITCH (0.03±0.65%, p=0.000). Significant improvements were noted in the mean changes in fasting glucose and AUCs of glucose in the ADD-ON vs. SWITCH (p=0.007 and p=0.000). Insulin secretion relative to glucose elevation (ISG; defined as AUC insulin/AUC glucose) increased significantly in the ADD-ON, although the mean change in fasting insulin level was significantly decreased in the ADD-ON (p=0.015 and p=0.026). The AUC of glucagon was significantly lower at 24-week relative to baseline in the ADD-ON, but was not significant in the two groups (p=0.047 and p=0.056, respectively). The combination therapy produced significant reductions in HbA1c, AUC of glucose and fasting glucose compared with switching to repaglinide without weight gain or severe hypoglycemia. The improved glycemic control with this combination therapy may be at least in part due to augmentation of repaglinide-induced insulin secretion by sitagliptin.
尽管西他列汀和瑞格列奈单药治疗可改善餐后高血糖，但二者联合使用的长期疗效和安全性尚未得到研究。在这项针对日本西他列汀控制不佳（糖化血红蛋白7.0 - 8.5%）患者的随机、为期24周的试验中，我们将40例患者随机分为两组，每组20例：一组为在西他列汀基础上加用瑞格列奈（ADD - ON组），另一组为将西他列汀换用瑞格列奈（SWITCH组）。在第0周和第24周进行了进餐耐量试验。主要结局指标为从基线到第24周糖化血红蛋白和葡萄糖曲线下面积（AUC）的变化。与SWITCH组（0.03±0.65%，p = 0.000）相比，ADD - ON组从基线到第24周糖化血红蛋白的平均变化更大（-0.87±0.63%，均值±标准差）。ADD - ON组与SWITCH组相比，空腹血糖和葡萄糖AUC的平均变化有显著改善（p = 0.007和p = 0.000）。尽管ADD - ON组空腹胰岛素水平的平均变化显著降低（p = 0.015和p = 0.026），但相对于葡萄糖升高的胰岛素分泌（ISG；定义为AUC胰岛素/AUC葡萄糖）在ADD - ON组显著增加。在ADD - ON组，相对于基线，24周时胰高血糖素的AUC显著降低，但两组间差异无统计学意义（分别为p = 0.047和p = 0.056）。与换用瑞格列奈相比，联合治疗使糖化血红蛋白、葡萄糖AUC和空腹血糖显著降低，且未出现体重增加或严重低血糖。这种联合治疗改善血糖控制可能至少部分归因于西他列汀增强了瑞格列奈诱导的胰岛素分泌。
