二甲双胍治疗的 2 型糖尿病患者中西格列汀加罗格列酮对胰岛β细胞功能和胰岛素敏感性的影响。
Effects of exenatide plus rosiglitazone on beta-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin.
机构信息
Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
出版信息
Diabetes Care. 2010 May;33(5):951-7. doi: 10.2337/dc09-1521. Epub 2010 Jan 27.
OBJECTIVE
Study the effects of exenatide (EXE) plus rosiglitazone (ROSI) on beta-cell function and insulin sensitivity using hyperglycemic and euglycemic insulin clamp techniques in participants with type 2 diabetes on metformin.
RESEARCH DESIGN AND METHODS
In this 20-week, randomized, open-label, multicenter study, participants (mean age, 56 +/- 10 years; weight, 93 +/- 16 kg; A1C, 7.8 +/- 0.7%) continued their metformin regimen and received either EXE 10 microg b.i.d. (n = 45), ROSI 4 mg b.i.d. (n = 45), or EXE 10 microg b.i.d. + ROSI 4 mg b.i.d. (n = 47). Seventy-three participants underwent clamp procedures to quantitate insulin secretion and insulin sensitivity. RESULTS A1C declined in all groups (P < 0.05), but decreased most with EXE+ROSI (EXE+ROSI, -1.3 +/- 0.1%; ROSI, -1.0 +/- 0.1%, EXE, -0.9 +/- 0.1%; EXE+ROSI vs. EXE or ROSI, P < 0.05). ROSI resulted in weight gain, while EXE and EXE+ROSI resulted in weight loss (EXE, -2.8 +/- 0.5 kg; EXE+ROSI, -1.2 +/- 0.5 kg; ROSI, + 1.5 +/- 0.5 kg; P < 0.05 between and within all groups). At week 20, 1st and 2nd phase insulin secretion was significantly higher in EXE and EXE+ROSI versus ROSI (both P < 0.05). Insulin sensitivity (M value) was significantly higher in EXE+ROSI versus EXE (P = 0.014).
CONCLUSIONS
Therapy with EXE+ROSI offset the weight gain observed with ROSI and elicited an additive effect on glycemic control with significant improvements in beta-cell function and insulin sensitivity.
目的
在服用二甲双胍的 2 型糖尿病患者中，使用高血糖和正常血糖胰岛素钳夹技术研究艾塞那肽（EXE）加罗格列酮（ROSI）对胰岛β细胞功能和胰岛素敏感性的影响。
研究设计和方法
在这项 20 周、随机、开放标签、多中心研究中，参与者（平均年龄 56±10 岁；体重 93±16kg；A1C7.8±0.7%）继续服用二甲双胍，并接受 EXE10μg，每日 2 次（n=45）、ROSI4mg，每日 2 次（n=45）或 EXE10μg+ROSI4mg，每日 2 次（n=47）治疗。73 名参与者进行了钳夹程序以定量胰岛素分泌和胰岛素敏感性。
结果
所有组的 A1C 均下降（P<0.05），但 EXE+ROSI 组下降最明显（EXE+ROSI，-1.3±0.1%；ROSI，-1.0±0.1%，EXE，-0.9±0.1%；EXE+ROSI 与 EXE 或 ROSI，P<0.05）。ROSI 导致体重增加，而 EXE 和 EXE+ROSI 导致体重减轻（EXE，-2.8±0.5kg；EXE+ROSI，-1.2±0.5kg；ROSI，+1.5±0.5kg；所有组之间和组内差异均有统计学意义（P<0.05））。在第 20 周时，与 ROSI 相比，EXE 和 EXE+ROSI 的第 1 相和第 2 相胰岛素分泌明显更高（均 P<0.05）。EXE+ROSI 的胰岛素敏感性（M 值）明显高于 EXE（P=0.014）。
结论
EXE+ROSI 治疗可抵消 ROSI 观察到的体重增加，并在改善β细胞功能和胰岛素敏感性方面产生协同作用，从而显著改善血糖控制。
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