Abstract
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, Clinical Trials.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. Protocol Registration: PROSPERO–CRD42023472186.
Published Version
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