title: Double-blind randomized clinical trial of the effects of ezetimibe on postprandial hyperlipidaemia and hyperglycaemia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Ezetimibe restored the postprandial dysregulation of lipid but did not affect glucose metabolism in a double-blind randomized crossover trial.
authors.affiliation: Department of Endocrinology & Metabolism, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Uru
authors.initials: U
authors.lastname: Nezu
authors.forename: Koji
authors.initials: K
authors.lastname: Inazumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Kanako
authors.initials: K
authors.lastname: Ono
authors.forename: Kazuki
authors.initials: K
authors.lastname: Orime
authors.forename: Jun
authors.initials: J
authors.lastname: Shirakawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Sato
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Koike
authors.forename: Tadashi
authors.initials: T
authors.lastname: Wakasugi
authors.forename: Misako
authors.initials: M
authors.lastname: Sato
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kawakami
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamakawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053283:Apolipoprotein B-48 / Q000378:metabolism; D001384:Azetidines / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000069438:Ezetimibe; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D006949:Hyperlipidemias / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D010919:Placebos; D019518:Postprandial Period; D011446:Prospective Studies; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D053283:Apolipoprotein B-48; D001384:Azetidines; D001786:Blood Glucose; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D010919:Placebos; D014280:Triglycerides; D002784:Cholesterol; D000069438:Ezetimibe; D005947:Glucose