Effects of GLP-1 receptor agonist therapy on resolution of steatohepatitis in non-alcoholic fatty liver disease: a systematic review and meta-analysis

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is common, can progress to cirrhosis and hepatic decompensation, and has no approved medical therapy in Canada. Objective: We conducted a systematic review on whether glucagon-like peptide-1 receptor agonists (GLP-1RA) improve non-alcoholic steatohepatitis (NASH) compared to standard care in NAFLD. Methods: We searched Medline Ovid, EMBASE(Elsevier), Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform in November 2023 for randomized controlled trials. Inclusion criteria included patients ≥13 years with NAFLD receiving GLP-1RA for ≥6 months compared to standard care/placebo. Cochrane risk-of-bias 2.0 tool was used for each outcome. After screening results in duplicate, we performed meta-analysis and reported odds ratios (OR) for dichotomous and mean difference of change score for continuous outcomes. Results: Six studies with 478 patients met inclusion criteria; 3 studies reported on the primary endpoint resolution of NASH. GLP-1RA likely leads to resolution of NASH (OR 4.45 (95% CI 1.92, 10.3)) and reduction in liver steatosis on imaging (–5.09% (95% CI −7.49, −2.69), but little to no reduction in liver stiffness on imaging (mean difference –0.17 kPa (95% CI −0.34, 0)). Interpretation: Treatment with GLP-1RA in NAFLD patients for ≥6 months can probably lead to improvement in NASH on liver biopsy and reduce liver steatosis on imaging. Whether improvements in steatosis on biopsy or imaging results in clinically significant outcomes need to be elucidated as the effects of GLP-1RA on liver fibrosis are unclear; larger ongoing trials may provide more definitive answers.