Pratley R E, Schweizer A, Rosenstock J, Foley J E, Banerji M A, Pi-Sunyer F X, Mills D, Dejager S
University of Vermont College of Medicine, Burlington, VT, USA.
Diabetes Obes Metab. 2008 Sep;10(10):931-8. doi: 10.1111/j.1463-1326.2007.00835.x. Epub 2007 Dec 17.
To assess the effects of 24-week treatment with vildagliptin on measures of beta-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM).
Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of beta-cell function [homeostasis model assessment of beta-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test-derived) measures of beta-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29).
In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AMDelta) = 10.3 +/- 1.5] and vs. placebo (between-treatment difference in AMDelta = 11.5 +/- 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AMDelta = -0.05 +/- 0.01) and vs. placebo (between-treatment difference in AMDelta = -0.09 +/- 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test-derived parameters, and ISR/G (between-treatment difference in AMDelta = 9.8 +/- 2.8 pmol/min/m(2)/mM, p < 0.001) and the insulinogenic index(0-peak glucose) (between-treatment difference in AMDelta = 0.24 +/- 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo.
Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test-derived measures of beta-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov.
评估在广泛的初治2型糖尿病（T2DM）患者中，使用维格列汀治疗24周对β细胞功能指标的影响。
汇总所有在初治T2DM患者中进行的双盲、多中心、随机、安慰剂对照或活性药物对照试验的数据，这些患者接受维格列汀单药治疗（每日100mg：每日两次，每次50mg或每日一次，100mg，n = 1855）或安慰剂（n = 347）。在总体汇总的单药治疗人群中评估β细胞功能的空腹指标[β细胞功能的稳态模型评估（HOMA-B）和胰岛素原：胰岛素比值]。在一部分患者的基线和第24周进行标准餐试验，评估维格列汀（每日100mg，n = 227）对β细胞功能的动态（餐试验衍生）指标[相对于葡萄糖的胰岛素分泌率（ISR/G）和胰岛素生成指数]相对于基线以及与安慰剂（n = 29）相比的影响。
在总体人群中，维格列汀相对于基线显著增加了HOMA-B[校正后平均变化（AMDelta）= 10.3±1.5]，与安慰剂相比也显著增加（AMDelta的组间差异 = 11.5±4.5，p = 0.01），并且相对于基线显著降低了胰岛素原：胰岛素比值（AMDelta = -0.05±0.01），与安慰剂相比也显著降低（AMDelta的组间差异 = -0.09±0.02，p < 0.001）。相对于基线，维格列汀单药治疗显著增加了所有餐试验衍生的参数，与安慰剂相比，ISR/G（AMDelta的组间差异 = 9.8±2.8 pmol/min/m²/mM，p < 0.001）和胰岛素生成指数（0-峰值葡萄糖）（AMDelta的组间差异 = 0.24±0.05 pmol/mmol，p = 0.045）显著增加。
在广泛的初治T2DM患者中，维格列汀单药治疗在空腹和餐试验衍生的β细胞功能指标方面均持续产生显著改善。所描述的所有III期试验（NCT 00099905、NCT 00099866、NCT 00099918、NCT 00101673、NCT 00101803和NCT 00120536）均已在ClinicalTrials.gov上注册。
