Effects of Epeleuton, a Novel Synthetic Second-Generation n-3 Fatty Acid, on Non-Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers.
Effects of Epeleuton, a Novel Synthetic Second-Generation n-3 Fatty Acid, on Non-Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers.
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DOI：
10.1161/jaha.119.016334
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发表时间：
2020-08-18
影响因子：
5.4
通讯作者：
Bhatt DL
中科院分区：
文献类型：
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作者：
Climax J;Newsome PN;Hamza M;Weissbach M;Coughlan D;Sattar N;McGuire DK;Bhatt DL
Epeleuton是15 -羟基二十碳五烯酸乙酯，是二十碳五烯酸的第二代合成n - 3脂肪酸衍生物。本研究的主要目的是通过对心脏代谢标志物的事后分析，评估爱培利顿对非酒精性脂肪性肝病（NAFLD）标志物的影响。在一项多中心、随机、双盲、安慰剂对照试验中，96名体重指数为25 ~ 40的非酒精性脂肪性肝病患者按1:1:1的比例随机接受爱普乐通2 g/天、爱普乐通1 g/天或安慰剂治疗16周。共有27%的患者患有糖尿病。第16周时，丙氨酸转氨酶和肝脏硬度变化的主要终点没有改善。二次分析和事后分析调查了心脏代谢标志物的变化。Epeleuton 2g /天显著降低甘油三酯、极低密度脂蛋白胆固醇和总胆固醇，而不增加低密度脂蛋白胆固醇。尽管平均基线血红蛋白A1C较低（HbA1C; 6.3±1.3%），但epeleuton 2 g/d显著降低HbA1C （- 0.4%； P=0.026）。在基线HbA1c为6.5%的患者中，2 g/天的eleleuton使HbA1c降低1.1% （P=0.047; n=26）。观察到空腹血糖、胰岛素和胰岛素抵抗指标的剂量依赖性降低。Epeleuton 2 g/d可降低心血管风险和内皮功能障碍的循环指标。Epeleuton耐受性良好，安全性与安慰剂没有区别。虽然epeleuton没有达到丙氨酸转氨酶或肝脏硬度的主要终点，但它显著降低了甘油三酯、HbA1C、血浆葡萄糖和炎症标志物。这些数据表明，epeleuton可能具有降低心血管风险和非酒精性脂肪性肝病的潜力，同时针对高甘油三酯血症、高血糖症和全身性炎症。进一步的试验正在计划中。网址：https://www.clini caltr ials.gov；唯一标识符：NCT02941549。
Epeleuton is 15‐hydroxy eicosapentaenoic acid ethyl ester, a second‐generation synthetic n‐3 fatty acid derivative of eicosapentaenoic acid. The primary objective was to assess the effect of epeleuton on markers of nonalcoholic fatty liver disease (NAFLD) with post hoc analyses of cardiometabolic markers. In a multicenter, randomized, double‐blind, placebo‐controlled trial, 96 adults with nonalcoholic fatty liver disease and body mass index 25 to 40 were randomized in a 1:1:1 ratio to receive epeleuton 2 g/day, epeleuton 1 g/day, or placebo for 16 weeks. A total of 27% of patients had diabetes mellitus. Primary end points of changes in alanine aminotransferase and liver stiffness did not improve at week 16. Secondary and post hoc analyses investigated changes in cardiometabolic markers. Epeleuton 2 g/day significantly decreased triglycerides, very‐low‐density lipoprotein cholesterol, and total cholesterol without increasing low‐density lipoprotein cholesterol. Despite a low mean baseline hemoglobin A1C (HbA1C; 6.3±1.3%), epeleuton 2 g/day significantly decreased HbA1c (−0.4%; P=0.026). Among patients with baseline HbA1c >6.5%, epeleuton 2 g/day decreased HbA1c by 1.1% (P=0.047; n=26). Consistent dose‐dependent reductions were observed for fasting plasma glucose, insulin, and insulin resistance indices. Epeleuton 2 g/day decreased circulating markers of cardiovascular risk and endothelial dysfunction. Epeleuton was well tolerated, with a safety profile not different from placebo. While epeleuton did not meet its primary end points on alanine aminotransferase or liver stiffness, it significantly decreased triglycerides, HbA1C, plasma glucose, and inflammatory markers. These data suggest epeleuton may have potential for cardiovascular risk reduction and nonalcoholic fatty liver disease by simultaneously targeting hypertriglyceridemia, hyperglycemia, and systemic inflammation. Further trials are planned. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02941549.