Göke Burkhard, Gause-Nilsson Ingrid, Persson Anders
Department of Internal Medicine II, University of Munich-Grosshadern, Marchinioninstr. 15, 81377 Munich, Germany.
Diab Vasc Dis Res. 2007 Sep;4(3):204-13. doi: 10.3132/dvdr.2007.041.
This study assessed the effects of tesaglitazar (0.5 or 1 mg/day), a dual peroxisome proliferator-activated receptor alpha/gamma agonist, when added to maximally tolerated metformin (2-2.5 g/day) in patients with poorly controlled type 2 diabetes. The primary end point of this 24-week, randomised, placebo-controlled study was the absolute change from baseline in glycosylated haemoglobin (HbA1C). Tesaglitazar significantly reduced HbA1C, fasting plasma glucose and insulin levels compared with placebo (p<0.0001 for all) when added to metformin. Triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C levels also improved with tesaglitazar treatment (p<0.0001 for all). Adverse events were generally similar across treatments, except for higher frequencies of peripheral oedema and weight gain in the tesaglitazar 1 mg group. Although reversibility was not fully evaluated, dose-dependent changes in mean serum creatinine levels and haematology measures tended to return towards baseline at follow-up. Despite the clinical discontinuation of tesaglitazar, this study has demonstrated the potential benefits of dual PPAR agonism as add-on therapy to metformin, in patients with poorly controlled type 2 diabetes.
本研究评估了替格列扎（0.5或1毫克/天），一种过氧化物酶体增殖物激活受体α/γ双重激动剂，添加到最大耐受剂量二甲双胍（2 - 2.5克/天）中，对2型糖尿病控制不佳患者的影响。这项为期24周的随机、安慰剂对照研究的主要终点是糖化血红蛋白（HbA1C）相对于基线的绝对变化。与安慰剂相比，替格列扎添加到二甲双胍治疗中时，显著降低了HbA1C、空腹血糖和胰岛素水平（所有p值均<0.0001）。替格列扎治疗还改善了甘油三酯水平、高密度脂蛋白胆固醇（HDL-C）和非HDL-C水平（所有p值均<0.0001）。除了替格列扎1毫克组外周水肿和体重增加的发生率较高外，各治疗组的不良事件总体相似。尽管未对可逆性进行全面评估，但平均血清肌酐水平和血液学指标的剂量依赖性变化在随访时倾向于恢复至基线水平。尽管替格列扎已停止临床应用，但本研究已证明，对于2型糖尿病控制不佳的患者，双重PPAR激动剂作为二甲双胍的附加治疗具有潜在益处。
