L-MARC Research Center, Louisville, Kentucky 40213, USA.
J Clin Endocrinol Metab. 2011 Sep;96(9):2889-97. doi: 10.1210/jc.2011-1061. Epub 2011 Jul 13.
Preclinical and clinical studies suggest that peroxisome proliferator-activated receptor (PPAR)-δ agonists favorably affect multiple metabolic parameters that are otherwise proatherogenic, many that are not optimally managed with statins alone.
The aim of this study was to evaluate the effects of MBX-8025 (a novel PPAR-δ agonist) on lipid and other metabolic parameters associated with increased atherosclerotic risk, administered alone and in combination with atorvastatin.
This was a randomized, double-blind, placebo-controlled, parallel group proof-of-concept study conducted at 30 U.S. research sites.
This study evaluated 181 overweight men and women with mixed dyslipidemia.
INTERVENTION(S): Subjects were administered once daily placebo, atorvastatin 20 mg, or MBX-8025 at 50 or 100 mg alone or combined with atorvastatin for 8 wk.
The main efficacy measures included change from baseline in apolipoprotein B-100, lipid levels, high-sensitivity C-reactive protein, and additional metabolic parameters, as well as the effect on the metabolic syndrome and LDL particle size.
Compared to placebo, MBX-8025 alone and in combination with atorvastatin significantly (P < 0.05) reduced apolipoprotein B-100 20-38%, LDL 18-43%, triglycerides 26-30%, non-high-density lipoprotein cholesterol 18-41%, free fatty acids 16-28%, and high-sensitivity C-reactive protein 43-72%; it raised high-density lipoprotein cholesterol 1-12% and also reduced the number of patients with the metabolic syndrome and a preponderance of small LDL particles. MBX-8025 was safe and generally well-tolerated. MBX-8025 also reduced liver enzyme levels.
MBX-8025, a novel PPAR-δ agonist, favorably affected multiple metabolic parameters with and without atorvastatin. A more complete understanding of MBX-8025 requires a larger future study.
临床前和临床研究表明，过氧化物酶体增殖物激活受体（PPAR）-δ激动剂可改善多种代谢参数，这些参数否则会促进动脉粥样硬化，其中许多参数仅用他汀类药物无法得到最佳控制。
本研究旨在评估 MBX-8025（一种新型 PPAR-δ激动剂）对单独使用和联合使用阿托伐他汀时与增加动脉粥样硬化风险相关的脂质和其他代谢参数的影响。
这是一项在美国 30 个研究地点进行的随机、双盲、安慰剂对照、平行组概念验证研究。
这项研究评估了 181 名超重的男性和女性，他们患有混合性血脂异常。
受试者每天一次给予安慰剂、阿托伐他汀 20mg 或 MBX-8025 50 或 100mg 单独或联合阿托伐他汀治疗 8 周。
主要疗效指标包括从基线开始的载脂蛋白 B-100、血脂水平、高敏 C 反应蛋白和其他代谢参数的变化，以及对代谢综合征和 LDL 颗粒大小的影响。
与安慰剂相比，MBX-8025 单独使用和联合使用阿托伐他汀可显著（P < 0.05）降低载脂蛋白 B-100 20-38%、LDL 18-43%、甘油三酯 26-30%、非高密度脂蛋白胆固醇 18-41%、游离脂肪酸 16-28%和高敏 C 反应蛋白 43-72%；升高高密度脂蛋白胆固醇 1-12%，并减少代谢综合征患者和小 LDL 颗粒优势的数量。MBX-8025 安全且一般耐受性良好。MBX-8025 还降低了肝酶水平。
新型 PPAR-δ 激动剂 MBX-8025 可改善有或无阿托伐他汀的多种代谢参数。对 MBX-8025 的更全面了解需要未来进行更大规模的研究。
