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

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• 作者：Jeffrey Cui¹ ; Len Philo² ; Phirum Nguyen¹ ; Heather Hofflich³ ; Carolyn Hernandez¹ ; Ricki Bettencourt¹ ; ⁴ ; Lisa Richards¹ ; ⁵ ; Joanie Salotti¹ ; ⁵ ; Archana Bhatt¹ ; Jonathan Hooker⁶ ; William Haufe⁶ ; Catherine Hooker⁶ ; David A. Brenner⁵ ; Claude B. Sirlin⁶ ; Rohit Loomba¹ ; ⁴ ; ⁵ ; ⁷ ; ^{roloomba@ucsd.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NAFLD ; non-alcoholic fatty liver disease ; NASH ; non-alcoholic steatohepatitis ; DPP-4 ; dipeptidyl peptidase 4 ; GLP-1 ; glucagon-like peptide-1 ; GIP ; glucose-dependent insulinotropic polypeptide ; HbA1c ; hemoglobin A1c ; SREBP-1c ; sterol regulatory element bind protein-1c ; T2DM ; type 2 diabetes mellitus ; ALT ; alanine aminotransferase ; AST ; aspartate aminotransferase ; GGT ; gamma-glutamyl transpeptidase ; MR ; magnetic resonance ; MRI ; magnetic resonance imaging ; MRI-PDFF ; MRI-proton density-fat fraction
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：65
• 期：2
• 页码：369-376
• 全文大小：1905 K

文摘

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 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&reg; 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.