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使用双（α/γ）过氧化物酶体增殖物激活受体激动剂muraglitazar改善二甲双胍单药治疗血糖控制不佳的2型糖尿病患者的血糖、甘油三酯及高密度脂蛋白胆固醇水平：一项双盲、随机、与吡格列酮对照的研究

Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: A double-blind, randomized, pioglitazone-comparative study.

作者信息

Kendall David M, Rubin Cindy J, Mohideen Pharis, Ledeine Jean-Marie, Belder Rene, Gross Jorge, Norwood Paul, O'Mahony Michael, Sall Kenneth, Sloan Greg, Roberts Anthony, Fiedorek Fred T, DeFronzo Ralph A

机构信息

International Diabetes Center and the University of Minnesota, Minneapolis, Minnesota, USA.

出版信息

Diabetes Care. 2006 May;29(5):1016-23. doi: 10.2337/diacare.2951016.

DOI:10.2337/diacare.2951016

PMID:16644631

Abstract

OBJECTIVE

We sought to evaluate the effects of muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor (PPAR) activator within the new glitazar class, on hyperglycemia and lipid abnormalities.

RESEARCH DESIGN AND METHODS

A double-blind, randomized, controlled trial was performed in 1,159 patients with type 2 diabetes inadequately controlled with metformin. Patients received once-daily doses of either 5 mg muraglitazar or 30 mg pioglitazone for a total of 24 weeks in addition to open-label metformin. Patients were continued in a double-blind fashion for an additional 26 weeks.

RESULTS

Analyses were conducted at week 24 for HbA1c (A1C) and at week 12 for lipid parameters. Mean A1C at baseline was 8.12 and 8.13% in muraglitazar and pioglitazone groups, respectively. At week 24, muraglitazar reduced mean A1C to 6.98% (-1.14% from baseline), and pioglitazone reduced mean A1C to 7.28% (-0.85% from baseline; P < 0.0001, muraglitazar vs. pioglitazone). At week 12, muraglitazar and pioglitazone reduced mean plasma triglyceride (-28 vs. -14%), apolipoprotein B (-12 vs. -6%), and non-HDL cholesterol (-6 vs. -1%) and increased HDL cholesterol (19 vs. 14%), respectively (P < 0.0001 vs. pioglitazone for all comparisons). At week 24, weight gain (1.4 and 0.6 kg, respectively) and edema (9.2 and 7.2%, respectively) were observed in the muraglitazar and pioglitazone groups; at week 50, weight gain and edema were 2.5 and 1.5 kg, respectively, and 11.8 and 8.9%, respectively. At week 50, heart failure was reported in seven patients (five with muraglitazar and two with pioglitazone), and seven deaths occurred: three from sudden death, two from cerebrovascular accident, and one from pancreatic cancer in the muraglitazar group and one from perforated duodenal ulcer in the pioglitazone group.

CONCLUSIONS

We found that 5 mg muraglitazar resulted in greater improvements in A1C and lipid parameters than a submaximal dose of 30 mg pioglitazone when added to metformin. Weight gain and edema were more common when muraglitazar was compared with a submaximal dose of pioglitazone.

摘要

目的

我们旨在评估新型格列他唑类药物muraglitazar（一种双（α/γ）过氧化物酶体增殖物激活受体（PPAR）激活剂）对高血糖和脂质异常的影响。

研究设计与方法

对1159例使用二甲双胍血糖控制不佳的2型糖尿病患者进行了一项双盲、随机、对照试验。除开放标签的二甲双胍外，患者接受每日一次剂量的5mg muraglitazar或30mg吡格列酮，共24周。患者以双盲方式继续治疗26周。

结果

在第24周对糖化血红蛋白（HbA1c）进行分析，在第12周对脂质参数进行分析。muraglitazar组和吡格列酮组基线时的平均HbA1c分别为8.12%和8.13%。在第24周时，muraglitazar将平均HbA1c降至6.98%（较基线降低1.14%），吡格列酮将平均HbA1c降至7.28%（较基线降低0.85%；muraglitazar与吡格列酮相比，P<0.0001）。在第12周时，muraglitazar和吡格列酮分别降低了平均血浆甘油三酯（-28%对-14%）、载脂蛋白B（-12%对-6%）和非高密度脂蛋白胆固醇（-6%对-1%），并增加了高密度脂蛋白胆固醇（19%对14%）（所有比较与吡格列酮相比，P<0.0001）。在第24周时，muraglitazar组和吡格列酮组分别观察到体重增加（分别为1.4kg和0.6kg）和水肿（分别为9.2%和7.2%）；在第50周时，体重增加和水肿分别为2.5kg和1.5kg，以及11.8%和8.9%。在第50周时，有7例患者报告发生心力衰竭（5例使用muraglitazar，2例使用吡格列酮），7例死亡：muraglitazar组中有3例猝死、2例脑血管意外和1例胰腺癌死亡，吡格列酮组中有1例十二指肠溃疡穿孔死亡。