Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Jan 10, 2017Clinics and research in hepatology and gastroenterology

Effectiveness and safety of diabetes drugs for non-alcoholic fatty liver disease

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Abstract

Among 329 patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), glucagon-like peptide-1 receptor agonists (GLP-1RAs) resulted in significant reductions in liver histology scores and gamma-glutamyl transpeptidase (GGT) levels.

GLP-1RAs decreased liver histology scores for steatosis by an average of 0.80 points, lobular inflammation by 0.22 points, hepatocellular ballooning by 0.41 points, and fibrosis by 0.35 points.
Treatment with GLP-1RAs led to a significant reduction in GGT levels by 13.8 U/L compared to placebo and positive agents.
Mild to moderate gastrointestinal discomfort was the major adverse event reported with GLP-1RA treatment, generally resolving within a few weeks.
Improvements in liver histology and reductions in aminotransferase levels were particularly noted in patients with diabetes.

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BACKGROUND AND OBJECTIVE: New drugs are urgently needed for the treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The aim of this meta-analysis was to evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in NAFLD/NASH.

METHODS: We searched the MEDLINE, Embase, and Cochrane Library Central to identify randomized controlled trials (RCTs) and observational studies that compared GLP-1RAs with a control treatment or baseline values with respect to efficacy and safety in patients with NAFLD/NASH. Mean differences (MDs) with 95% confidence intervals (CIs) and odds ratios (ORs) were pooled using a random-effect model.

RESULTS: Six studies were eligible and included. Among the 329 NAFLD/NASH patients included in these studies, 277 patients had type 2 diabetes (T2D). GLP-1RA treatment produced significant reductions relative to baseline in liver histology scores for steatosis (MD, 0.80; 95% CI, 0.49 to 1.11), lobular inflammation (MD, 0.22; 95% CI, 0.00 to 0.45), hepatocellular ballooning (MD, 0.41; 95% CI, 0.15 to 0.67) and fibrosis (MD, 0.35; 95% CI, 0.00 to 0.70). Compared with placebo and positive agents, GLP-1RAs significantly reduced gamma-glutamyl transpeptidase (GGT) levels (MD, 13.8 U/L; 95% CI, 7.4 to 20.3; P<0.001). The reported major adverse events associated with GLP-1RA treatment included mild to moderate gastrointestinal discomfort that resolved within a few weeks.

CONCLUSIONS: Our study suggests that in NASH patients, particularly patients with diabetes, GLP-1RAs may improve liver histology and reduce aminotransferase levels from baseline. Benefits of GLP-1RAs are considered to outweigh the risks in NAFLD/NASH patients with or without diabetes.

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Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: A systematic review and meta-analysis

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