Authors: Jeffrey Cui, Len Philo, Phirum Nguyen, Heather Hofflich, Carolyn Hernandez, Ricki Bettencourt, Lisa Richards, Joanie Salotti, Archana Bhatt, Jonathan Hooker, William Haufe, Catherine Hooker, David A. Brenner, Claude B. Sirlin, Rohit Loomba
Summary:
Background & Aims: Uncontrolled studies show sitagliptin, an oral DPP-4 inhibitor, may improve alanine aminotransferase and liver histology in nonalcoholic 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 100 mg/day or placebo for 24 weeks. 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 r2 = 0.96 to r2 = 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 nonalcoholic 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 nonalcoholic fatty liver disease clinical trials.
Source:
Journal of Hepatology; 2016