Department of Endocrinology & Metabolism, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
J Atheroscler Thromb. 2012;19(12):1093-101. doi: 10.5551/jat.12427. Epub 2012 Aug 9.
Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 (NPC1L1) and reducing LDL cholesterol (LDL-C). In animals, ezetimibe reversed diet-induced obesity, liver steatosis, and insulin resistance. In humans, its potential effects on liver steatosis and insulin resistance have been suggested. We investigated the effects of ezetimibe on postprandial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind randomized crossover trial.
Twenty obese men with hypertriglyceridaemia were assigned randomly to an ezetimibe- or a placebo-precedence-treated group. Subjects in the ezetimibe group were treated with ezetimibe (10 mg/day) for the first 4 weeks, followed by a 4-week interval and then treated with placebo for another 4 weeks. The placebo group received these treatments in reverse order. Subjects were requested to fast for at least 12 hours and then received a standard meal. Blood samples were collected at 0, 30, 60, 120, 240, 360 and 480 minutes after the meal on Days 0, 28, 56 and 84 and were used to measure the lipid and glucose metabolism markers.
Ezetimibe significantly decreased the postprandial serum triglyceride excursion (p=0.01) and fasting serum LDL-C, remnant-like particles(RLP) and ApoB48 levels (p<0.05). Postprandial glucose excursion, serum insulin levels, serum glucose-dependent insulinotropic polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) were not significantly affected by ezetimibe treatment.
Ezetimibe restored the postprandial dysregulation of lipid but did not affect glucose metabolism in a double-blind randomized crossover trial.
依折麦布通过抑制 NPC1L1 来选择性阻断肠道胆固醇吸收，从而降低 LDL 胆固醇（LDL-C）。在动物模型中，依折麦布可逆转饮食诱导的肥胖、肝脂肪变性和胰岛素抵抗。在人类中，其对肝脂肪变性和胰岛素抵抗的潜在影响已被提出。我们在一项双盲随机交叉试验中，研究了依折麦布对伴有血脂异常的肥胖患者餐后高脂血症和高血糖的影响。
20 名伴有高甘油三酯血症的肥胖男性被随机分配到依折麦布或安慰剂预处理组。依折麦布组在第 1 至 4 周接受依折麦布（10 mg/天）治疗，然后间隔 4 周，再接受 4 周安慰剂治疗。安慰剂组以相反的顺序接受这些治疗。要求受试者禁食至少 12 小时，然后给予标准餐。在第 0、28、56 和 84 天，在 0、30、60、120、240、360 和 480 分钟时采集空腹和餐后血样，以测量脂质和葡萄糖代谢标志物。
依折麦布显著降低了餐后血清甘油三酯的波动（p=0.01）和空腹血清 LDL-C、残粒样颗粒（RLP）和 ApoB48 水平（p<0.05）。依折麦布治疗对餐后血糖波动、血清胰岛素水平、血清葡萄糖依赖性胰岛素释放肽（GIP）和活性胰高血糖素样肽-1（GLP-1）没有显著影响。
依折麦布在一项双盲随机交叉试验中恢复了餐后脂质的失调，但对葡萄糖代谢没有影响。
