Sitagliptin was not superior to placebo in reducing liver fat in prediabetic or diabetic patients with nonalcoholic fatty liver disease (NAFLD), according to a study published in the Journal of Hepatology.   

There are currently no treatments approved for NAFLD. Previous uncontrolled studies demonstrated that sitagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor may improve alanine aminotransferase (ALT) and liver histology in patients with NAFLD. Rohit Loomba, MD, from the UC San Diego School of Medicine, and colleagues conducted a randomized, double-blind, allocation-concealed, placebo-controlled trial to compare the efficacy of sitagliptin vs. placebo in reducing liver fat measured by MRI-derived proton density-fat fraction (MRI-PDFF).

Fifty patients with NAFLD who were prediabetic or diabetic were randomized to oral sitagliptin 100mg daily or placebo for 24 weeks. Primary outcome was the change in liver fat measured by MRI-PDFF in co-localized regions of interest. Other assessments included MR spectroscopy (MRS) for internal validation of MRI-PDFF’s accuracy, and MR elastography (MRE) and FIBROSpect II to study liver fibrosis. 

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The study data showed sitagliptin was not significantly better than placebo in reducing liver fat (mean difference –1.3%; P=0.4). No significant differences in end-of-treatment MRI-PDFF compared to baseline were observed for sitagliptin (18.1% to 16.9%; P=0.27) or for placebo (16.6% to 14%; P=0.07). The two study arms exhibited no significant differences for changes in ALT, aspartate aminotransferase, low-density lipoprotein, homeostatic model assessment insulin resistance, and MRE-derived liver stiffness. 

Although the study findings did not support previous research that sitagliptin was effective for NAFLD, it shows new evidence that clinical studies with patients at higher risk for diabetes do not necessarily require a liver biopsy to be efficiently screened for potential therapeutic agents. Dr. Loomba added, “”MRI-PDFF, and magnetic resonance elastography proved to be accurate, quantitative, and useful over the study duration in measuring the state and progression of disease. These technologies should be further investigated in clinical trials, especially those of longer duration.

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