Kudo-Fujimaki Kyoko, Hirose Takahisa, Yoshihara Tomoaki, Sato Fumihiko, Someya Yuki, Ohmura Chie, Kanazawa Akio, Fujitani Yoshio, Watada Hirotaka
Department of Metabolism and Endocrinology Toho University School of Medicine Tokyo Japan.
Department of Metabolism and Endocrinology Toho University School of Medicine Tokyo Japan ; Division of Diabetes, Metabolism and Endocrinology Department of Medicine Toho University School of Medicine Tokyo Japan.
J Diabetes Investig. 2014 Jul;5(4):400-9. doi: 10.1111/jdi.12160. Epub 2013 Nov 5.
AIMS/INTRODUCTION: To investigate the efficacy and safety of vildagliptin, a potent dipeptidyl peptidase-4 inhibitor, as add-on to nateglinide, compared with switching to vildagliptin in Japanese type 2 diabetes patients poorly controlled with nateglinide.
A total of 40 patients inadequately controlled with nateglinide were randomized to the switching group (n = 20, switching from nateglinide to vildagliptin) or combination group (n = 20, nateglinide plus vildagliptin). A meal tolerance test was carried out at weeks 0 and 24.
The mean changes in glycated hemoglobin from baseline to week 24 were -1.2 ± 0.3% and -0.3 ± 0.5% in patients of the combination and switching groups, respectively, and the difference between the groups was statistically significant (P < 0.001). The mean changes in area under the curve of glucose from 0 to 180 min (AUC0-180 min) from baseline to week 24 was -361 ± 271.3 mmol·min/L in patients of the combination group compared with 141 ± 241.9 mmol·min/L in those of the switching group (P < 0.001). The incidence of hypoglycemic events was low (three in the combination group), and none of the patients developed severe hypoglycemia. Although the addition of vildagliptin to nateglinide did not significantly increase insulin secretion relative to glucose elevation (ISG) after meal load (ISG0-180 min: AUC0-180 min insulin / AUC0-180 min glucose) in comparison with that in baseline, the mean ISG0-30 min 24 weeks after addition of vildagliptin to nateglinide was significantly higher than that at baseline. In contrast, switching from nateglinide to vildagliptin reduced the mean ISG0-180 min, relative to baseline.
The combination therapy of vildagliptin and nateglinide is effective and safe in Japanese type 2 diabetes, and the improved glycemic control is as a result of augmentation of nateglinide-induced early phase insulin secretion. This trial was registered with UMIN (no. ID000004010).
目的/引言：研究强效二肽基肽酶-4抑制剂维格列汀作为那格列奈的附加治疗药物的疗效和安全性，并与在那格列奈治疗效果不佳的日本2型糖尿病患者中换用维格列汀进行比较。
共有40例使用那格列奈控制不佳的患者被随机分为换药组（n = 20，从那格列奈换用维格列汀）或联合治疗组（n = 20，那格列奈加维格列汀）。在第0周和第24周进行了糖耐量试验。
联合治疗组和换药组患者从基线到第24周糖化血红蛋白的平均变化分别为-1.2±0.3%和-0.3±0.5%，两组间差异具有统计学意义（P < 0.001）。联合治疗组患者从基线到第24周0至180分钟葡萄糖曲线下面积（AUC0-180分钟）的平均变化为-361±271.3 mmol·min/L，而换药组为141±241.9 mmol·min/L（P < 0.001）。低血糖事件发生率较低（联合治疗组3例），且无患者发生严重低血糖。虽然与基线相比，那格列奈加用维格列汀后餐后负荷后相对于血糖升高的胰岛素分泌（ISG）（ISG0-180分钟：AUC0-180分钟胰岛素/AUC0-180分钟葡萄糖）没有显著增加，但那格列奈加用维格列汀24周后平均ISG0-30分钟显著高于基线水平。相反，从那格列奈换用维格列汀使平均ISG0-180分钟相对于基线降低。
维格列汀与那格列奈联合治疗对日本2型糖尿病有效且安全，血糖控制改善是那格列奈诱导的早期胰岛素分泌增加的结果。本试验在UMIN注册（编号ID000004010）。
