《临床内分泌学与新陈代谢杂志》(Journal of Clinical Endocrinology & Metabolism)近期发表了一项研究结果，一项Ⅱ期概念验证研究表明，当单独应用他汀类药物时，添加在研药物MBX-8025可能有助于控制血脂和其他代谢指标。
MBX-8025是一种PPAR(过氧化物酶体增殖子激活受体)-δ激动剂。美国路易斯维尔L - MARC研究中心Bays博士和其同事，随机分配181例体重超重且血脂异常的男性和女性接受6种每日治疗方案:单独50mg或100mg MBX-8025，单独阿托伐他汀20mg，一个或其他剂量的MBX-8025联合阿托伐他汀，或者安慰剂。
试验结果显示，与安慰剂组相比，在所有治疗组中，MBX-8025都显着降低了载脂蛋白B-100的水平。两种剂量的MBX-8025可使载脂蛋白B-100减少20%，而阿托伐他汀可使载脂蛋白B-100减少34%，联合治疗使载脂蛋白B-100减少32%~38%。
50mg和100mg的MBX-8025分别使LDL-C降低了18%和22%;阿托伐他汀使LDL-C降低了41%;联合治疗使LDL-C降低了40%~43%(所有均与安慰剂相比)。
再次与安慰剂相比，两个剂量的MBX-8025单一治疗均使甘油三酯降低了26%~30%，阿托伐他汀使甘油三酯降低了14%。
此外，与安慰剂或阿托伐他汀单药相比，MBX-8025使代谢综合征的患病率降低了14%~29%。它还使有小LDL颗粒优势患者的人数减少了10%~20%。
研究人员说，各组的整体不良反应大致相同，但需要更大规模的研究来完全了解MBX-8025的安全性。
生物探索推荐英文论文摘要：
MBX-8025, A Novel Peroxisome Proliferator Receptor-δ Agonist: Lipid and Other Metabolic Effects in Dyslipidemic Overweight Patients Treated with and without Atorvastatin
Context: 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.
Objective: 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.
Design and Setting: This was a randomized, double-blind, placebo-controlled, parallel group proof-of-concept study conducted at 30 U.S. research sites.
Participants: 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.
Main Outcome Measures: 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.
Results: 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.
Conclusion: 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.
