title: Effects of the new dual PPAR α/δ agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism.
abstract: OBJECTIVE
  We evaluated the metabolic effects and tolerability of GFT505, a novel dual peroxisome proliferator-activated receptor α/δ agonist, in abdominally obese patients with either combined dyslipidemia or prediabetes.
  
  
  METHODS
  The S1 study was conducted in 94 patients with combined dyslipidemia while the S2 study was conducted in 47 patients with prediabetes. Participants were randomly assigned in a double-blind manner to GFT505 at 80 mg/day or placebo for 28 (S1) or 35 (S2) days. Primary efficacy end points were changes from baseline at week 4 in both fasting plasma triglycerides and HDL cholesterol in the S1 group and 2-h glucose upon oral glucose tolerance test in the S2 group.
  
  
  RESULTS
  In comparison with placebo, GFT505 significantly reduced fasting plasma triglycerides (S1: least squares means -16.7% [95% one-sided CI -∞ to -5.3], P = 0.005; S2: -24.8% [-∞ to -10.5], P = 0.0003) and increased HDL cholesterol (S1: 7.8% [3.0 to ∞], P = 0.004; S2: 9.3% [1.7 to ∞], P = 0.009) in both studies, whereas LDL cholesterol only decreased in S2 (-11.0% [ -∞ to -3.5], P = 0.002). In S2, GFT505 did not reduce 2-h glucose (-0.52 mmol/L [-∞ to 0.61], P = 0.18) but led to a significant decrease of homeostasis model assessment of insulin resistance (-31.4% [-∞ to 12.5], P = 0.001), fasting plasma glucose (-0.37 mmol/L [-∞ to -0.10], P = 0.01) and fructosamine (-3.6% [-∞ to -0.20], P = 0.02). GFT505 also reduced γ glutamyl transferase levels in both studies (S1: -19.9% [-∞ to -12.8], P < 0.0001; S2: -15.1% [-∞ to -1.1], P = 0.004). No specific adverse safety signals were reported during the studies.
  
  
  CONCLUSIONS
  GFT505 may be considered a new drug candidate for the treatment of lipid and glucose disorders associated with the metabolic syndrome.
authors.affiliation: Department of Endocrinology, L'institut du Thorax, Nantes University Hospital, Nantes, France. bertrand.cariou@univ-nantes.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Cariou
authors.forename: Yassine
authors.initials: Y
authors.lastname: Zaïr
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
mesh_terms: D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D047188:Chalcones / Q000627:therapeutic use*; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists*; D047494:PPAR delta / Q000819:agonists*; D011236:Prediabetic State / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D011422:Propionates / Q000627:therapeutic use*
chemical_list: C585906:2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid; D019440:Anti-Obesity Agents; D047188:Chalcones; D000960:Hypolipidemic Agents; D008055:Lipids; D047493:PPAR alpha; D047494:PPAR delta; D011422:Propionates; D005947:Glucose