Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: an open-label randomized controlled trial (ESSENTIAL study)

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD).</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; <jats:italic>p</jats:italic> = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; <jats:italic>p</jats:italic> < 0.001 and 15.0 to 12.4%; <jats:italic>p</jats:italic> = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, <jats:italic>p</jats:italic> > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; <jats:italic>p</jats:italic> = 0.018), but not in the monotherapy group (323 to 311 dB/m; <jats:italic>p</jats:italic> = 0.104).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population.</jats:p> </jats:sec><jats:sec> <jats:title>Trial registration</jats:title> <jats:p>The trial was registered at ClinicalTrials.gov (registration number: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03434613">NCT03434613</jats:ext-link>).</jats:p> </jats:sec>