title: Does rimonabant independently affect free fatty acid and glucose metabolism?
abstract: BACKGROUND
  Endocannabinoid receptor 1 blockade is proposed to improve metabolic complications of obesity via central and peripheral effects.
  
  
  OBJECTIVE
  Our objective was to test whether rimonabant improves insulin regulation of free fatty acid and glucose metabolism after controlling for fat loss.
  
  
  METHODS
  This was a double-blind, placebo-controlled substudy of the visceral fat reduction assessed by computed tomography scan on rimonabant (VICTORIA) trial.
  
  
  METHODS
  Sixty-seven abdominally obese, metabolic syndrome volunteers age 35-70 yr participated at academic medical center general clinical research centers.
  
  
  METHODS
  Intervention included a 12-month lifestyle weight management program plus rimonabant 20 mg/d or placebo.
  
  
  METHODS
  Body composition and two-step euglycemic, hyperinsulinemic clamp before and after intervention were performed. Insulin sensitivity was assessed as insulin concentration needed to suppress by 50% palmitate concentration [IC50(palmitate)], flux [IC50(palmitate)f], and hepatic glucose output [IC50(HGO)] and as insulin-stimulated glucose disposal (Δ glucose disappearance per Δ insulin concentration--glucose slope).
  
  
  RESULTS
  Body fat decreased by 4.5±2.9% (SD) in the rimonabant and 1.9±4.5% in the placebo group (P<0.005). The primary [improvement in IC50(palmitate) and IC50(palmitate)f] and secondary [improvement in IC50(HGO) and glucose slope] outcomes were not significantly different between the rimonabant and placebo groups. Post hoc analyses revealed that 1) changes in body mass index (BMI) and IC50(palmitate) were correlated (P=0.005) in the rimonabant group; this relationship was not significantly different from placebo when controlling for greater BMI loss (P=0.5); 2) insulin-regulated glucose disposal improved in both groups (P=0.002) and correlated with changes in BMI.
  
  
  CONCLUSIONS
  Improvements observed in insulin regulation of free fatty acid and glucose metabolism with rimonabant treatment in humans was not greater than that predicted by weight loss alone.
authors.affiliation: Endocrine Research Unit, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Triay
authors.forename: Manpreet
authors.initials: M
authors.lastname: Mundi
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.forename: Frederico G
authors.initials: FG
authors.lastname: Toledo
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.forename: Haitham
authors.initials: H
authors.lastname: Abu-Lebdeh
authors.forename: Michael
authors.initials: M
authors.lastname: Jensen
mesh_terms: D000328:Adult; D000368:Aged; D001521:Behavior Therapy; D001823:Body Composition / Q000187:drug effects; D063387:Cannabinoid Receptor Antagonists; D004038:Diet, Reducing; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism; D008019:Life Style; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy*; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077285:Rimonabant; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
chemical_list: D063387:Cannabinoid Receptor Antagonists; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010880:Piperidines; D011720:Pyrazoles; D005947:Glucose; D000077285:Rimonabant