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Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial.

  • Author(s): Cui, Jeffrey
  • Philo, Len
  • Nguyen, Phirum
  • Hofflich, Heather
  • Hernandez, Carolyn
  • Bettencourt, Ricki
  • Richards, Lisa
  • Salotti, Joanie
  • Bhatt, Archana
  • Hooker, Jonathan
  • Haufe, William
  • Hooker, Catherine
  • Brenner, David A
  • Sirlin, Claude B
  • Loomba, Rohit
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081213/pdf/nihms-790802.pdf
No data is associated with this publication.
Abstract

BACKGROUND & AIMS: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). METHODS: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. RESULTS: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). CONCLUSIONS:Sitagliptin was safe but not better than placebo in reducing liver fat in prediabetic or diabetic patients with NAFLD. LAY SUMMARY: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.

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