title: Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial.
abstract: Uncontrolled studies show sitagliptin, an oral DPP-4 inhibitor, may improve alanine aminotransferase and liver histology in non-alcoholic fatty liver disease (NAFLD) patients. We aimed to compare sitagliptin vs. the efficacy of a placebo in reducing liver fat measured by MRI-derived proton density-fat fraction (MRI-PDFF).
  
  
  
  This randomized, double-blind, allocation-concealed, placebo-controlled trial included 50 NAFLD patients with prediabetes or early diabetes randomized to sitagliptin orally 100mg/day or placebo for 24weeks. Primary outcome was liver fat change measured by MRI-PDFF in colocalized regions of interest within each of nine liver segments. Additional advanced assessments included MR spectroscopy (MRS) for internal validation of MRI-PDFF's accuracy, and magnetic resonance elastography (MRE) and FIBROSpect® II to assess liver fibrosis.
  
  
  
  Sitagliptin was not significantly better than placebo in reducing liver fat measured by MRI-PDFF (mean difference between sitagliptin and placebo arms: -1.3%, p=0.4). Compared to baseline, there were no significant differences in end-of-treatment MRI-PDFF for sitagliptin (18.1% to 16.9%, p=0.27) or placebo (16.6% to 14.0%, p=0.07). The groups had no significant differences for changes in alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, homeostatic model assessment insulin resistance, and MRE-derived liver stiffness. In both groups at baseline and post-treatment, MRI-PDFF and MRS showed robust correlation coefficients ranging from r(2)=0.96 to r(2)=0.99 (p<0.0001), demonstrating the strong internal validity of the findings. FIBROSpect® II showed no changes in the sitagliptin group but was significantly increased in the placebo group (p=0.03).
  
  
  
  Sitagliptin was safe but not better than placebo in reducing liver fat in prediabetic or diabetic patients with NAFLD.
  
  
  
  In a randomized, double-blind, placebo-controlled study, the anti-diabetic drug sitagliptin was no more effective than placebo for improving liver fat and liver fibrosis in patients with non-alcoholic fatty liver disease. This study demonstrates that non-invasive magnetic resonance imaging techniques, including magnetic resonance imaging-proton density-fat fraction and magnetic resonance elastography, can be used to assess treatment response in non-alcoholic fatty liver disease clinical trials.
authors.affiliation: NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cui
authors.affiliation: Naval Medical Center San Diego, San Diego, CA, United States.
authors.forename: Len
authors.initials: L
authors.lastname: Philo
authors.affiliation: NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Phirum
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Division of General Internal Medicine, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Hofflich
authors.affiliation: NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hernandez
authors.affiliation: NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States; Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Ricki
authors.initials: R
authors.lastname: Bettencourt
authors.affiliation: NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States; Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Richards
authors.affiliation: NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States; Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Joanie
authors.initials: J
authors.lastname: Salotti
authors.affiliation: NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Archana
authors.initials: A
authors.lastname: Bhatt
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hooker
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, United States.
authors.forename: William
authors.initials: W
authors.lastname: Haufe
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hooker
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Brenner
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, United States.
authors.forename: Claude B
authors.initials: CB
authors.lastname: Sirlin
authors.affiliation: NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, United States; Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, United States; Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, United States; San Diego Integrated NAFLD Research Consortium (SINC), United States. Electronic address: roloomba@ucsd.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
mesh_terms: D004311:Double-Blind Method; D054459:Elasticity Imaging Techniques; D006801:Humans; D008099:Liver; D008279:Magnetic Resonance Imaging; D065626:Non-alcoholic Fatty Liver Disease; D000068900:Sitagliptin Phosphate
chemical_list: D000068900:Sitagliptin Phosphate
keywords: Biomarker; Fat mapping; Fibrosis; Hepatic steatosis; Imaging; Lipid lowering therapy; MRI-proton-density-fat-fraction (PDFF); Magnetic resonance elastography; NAFLD; Non-alcoholic steatohepatitis; Non-invasive assessment; Sitagliptin