One Year's Treatment with the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide Decreases Hepatic Fat Content in Women with Nonalcoholic Fatty Liver Disease and Prior Gestational Diabetes Mellitus in a Randomized, Placebo-Controlled Trial.

Louise Vedtofte,Lise L Gluud,Peter M Gørtz,Peter Damm,Jens J Holst,Tine D Clausen,Camilla Andreasen,Tina Vilsbøll,Signe Foghsgaard,Elisabeth R Mathiesen,Henning Grønbæk,Emilie Bahne,Jonatan I Bagger,Jens A Svare,Filip K Knop,Charlotte Strandberg

doi:10.3390/jcm9103213

Abstract

Prior gestational diabetes mellitus (pGDM) is associated with increased risk of nonalcoholic fatty liver disease (NAFLD). Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists has shown beneficial effects in NAFLD patients. We evaluated the effect of the GLP-1 analogue liraglutide on NAFLD features in women with pGDM. Eighty-two overweight/obese, nondiabetic women with pGDM were included. We performed abdominal ultrasound, transient elastography with controlled attenuation parameter (CAP), and blood sampling at baseline and after 1 year. Thirty-seven women were randomized to liraglutide (1.8 mg once-daily) and 45 to placebo. Based on the ultrasound scan, 18 women (22%) had ultrasound-verified NAFLD at baseline and of these, 10 (56%) received liraglutide treatment. After 1 year, eight participants no longer had steatosis, four in each treatment group. The number of participants who developed NAFLD was similar in the two treatment groups; five in the liraglutide group and six in the placebo group (p = 0.74). Compared to placebo, liraglutide reduced the CAP-assessed intrahepatic fat content (−28 (−44;−11) vs. 2 (−13;18) dB/m, p < 0.01) and body weight (−4.7 (−6.4;−2.9) vs. −1.4 (−3;0.3) kg, p < 0.01). One-year’s liraglutide treatment had no effect on the presence of ultrasound-diagnosed NAFLD in overweight/obese nondiabetic women with pGDM, but reduced body weight and steatosis assessed by transient elastography with CAP.

Highlights

Obesity, type 2 diabetes, dyslipidemia, and insulin resistance are closely associated with nonalcoholic fatty liver disease (NAFLD) [1,2]
NAFLD covers a spectrum of conditions ranging from simple steatosis over nonalcoholic steatohepatitis (NASH), which may lead to fibrosis and cirrhosis [3]
Additional objectives included estimation of change from baseline to year one in circulating liver enzymes, inflammatory markers, cholesterols, glucagon, and steatosis measured by transient elastography; controlled attenuation parameter (CAP) as measured by the FibroScan®; fatty liver index (FLI), whole body and visceral fat mass, and android-to-gynoid fat mass ratio measured by dual energy X-ray absorptiometry (DXA) scan

Summary

Introduction

Type 2 diabetes, dyslipidemia, and insulin resistance are closely associated with nonalcoholic fatty liver disease (NAFLD) [1,2]. NAFLD covers a spectrum of conditions ranging from simple steatosis over nonalcoholic steatohepatitis (NASH), which may lead to fibrosis and cirrhosis [3]. NAFLD is currently the most common chronic liver disease in the Western world [4] with a prevalence of 20–33% among adults [5] and up to 70% in adults with type 2 diabetes [6]. NAFLD is strongly associated with cardiovascular disease, which is the leading cause of death in patients with NAFLD and NASH with fibrosis [7]. Biomarkers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), soluble CD163 (sCD163), are being used for noninvasive monitoring of hepatic inflammation, injury, and recovery [8,9]

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Conclusion