Wilding John P H, Gause-Nilsson Ingrid, Persson Anders
Clinical Sciences Centre, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, UK.
Diab Vasc Dis Res. 2007 Sep;4(3):194-203. doi: 10.3132/dvdr.2007.040.
This randomised, double-blind, parallel-group, multicentre study investigated the effects of the dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, tesaglitazar (0.5 and 1 mg), as add-on treatment in 568 patients with type 2 diabetes that was poorly controlled with sulphonylurea therapy titrated to the highest tolerated dose. There was a significant placebo-corrected reduction in glycosylated haemoglobin (HbA1C) from baseline to week 24 with tesaglitazar 0.5 mg and 1 mg (mean [95% confidence interval]: -0.93% [-1.09, -0.77] and -1.3% [-1.46, -1.14]; p<0.0001). Significant reductions were observed in insulin, fasting plasma glucose (FPG), triglyceride (all p<0.001) and non-high-density lipoprotein (HDL) cholesterol (p<0.001). Tesaglitazar increased levels of HDL-cholesterol (p<0.0001), adiponectin (p<0.0001) and leptin (p<0.001), but was associated with dose-dependent increases in serum creatinine and decreases in haemoglobin. This study showed improvements in glycaemic control and dyslipidaemia in patients with type 2 diabetes poorly controlled with existing sulphonylurea therapy. Although tesaglitazar has now been discontinued from clinical development, these results remain relevant to future research into PPAR agonists.
这项随机、双盲、平行组、多中心研究调查了双重过氧化物酶体增殖物激活受体（PPAR）α/γ激动剂替格列扎（0.5毫克和1毫克）作为附加治疗对568例使用磺脲类药物治疗且剂量已滴定至最大耐受剂量但血糖控制不佳的2型糖尿病患者的影响。与基线相比，在第24周时，0.5毫克和1毫克替格列扎组糖化血红蛋白（HbA1C）经安慰剂校正后有显著降低（均值[95%置信区间]：-0.93%[-1.09，-0.77]和-1.3%[-1.46，-1.14]；p<0.0001）。胰岛素、空腹血糖（FPG）、甘油三酯（均p<0.001）和非高密度脂蛋白（HDL）胆固醇（p<0.001）均有显著降低。替格列扎可提高HDL胆固醇（p<0.0001）、脂联素（p<0.0001）和瘦素（p<0.001）水平，但与血清肌酐剂量依赖性升高和血红蛋白降低有关。这项研究表明，对于现有磺脲类药物治疗血糖控制不佳的2型糖尿病患者，其血糖控制和血脂异常情况有所改善。尽管替格列扎现已停止临床开发，但这些结果仍与未来PPAR激动剂的研究相关。
