GLP-1 RECEPTOR AGONISTS AND NON-ALCOHOLIC FATTY LIVER DISEASE: EFFICACY IN STEATOSIS RESOLUTION - A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a very common metabolic liver disease for which there are limited pharmacological treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are commonly used in the treatment of type 2 diabetes and obesity; however, the effects on hepatic steatosis have not been fully synthesized with varied evidence found at randomized controlled trials (RCTs).

Objectives: To systematically review and quantitatively synthesize evidence from randomized controlled trials assessing the efficacy of GLP-1 receptor agonists for the reduction of hepatic steatosis in individuals with either hepatic steatosis (NALD) or non-alcoholic steatohepatitis (NASH).

Methods: A systematic review and meta-analysis was performed according to PRSMA 2020 guidelines. Randomized controlled trials evaluating GLP-1 receptor agonists in adult patients with either type of liver disease (NAD or NASH) were included. The major outcome was change in hepatic steatosis at the end of the treatment assessed by imaging based or quantitative modalities, using standardized mean difference (SMD, Hedges g) pooled. A random effects model was used. Risk of bias was evaluated by using the Cochrane RoB 2 tool. Heterogeneity was assessed by using the I² statistic.

Results:

Five randomized controlled trials were included in the systematic review, out of which three included extractable continuous data for the quantitative synthesis. These trials assessed liraglutide or dulaglutide over 24-26 week follow up durations and measured hepatic steatosis with MRI-based or quantitative imaging over time. The pooled analysis showed the statistically significant decrease in hepatic steatosis when using GLP-1 receptor agonist versus control (SMD -0.46; 95% CI -0.86 to -0.07; p = 0.022). The level of between-study heterogeneity was low (I² = 0 percent). The pooled effect was found strong and directional, which was ensured by sensitivity analyses. Risk of bias was low to moderate overall and risk was mainly due to open-label study designs.

Conclusions:

GLP-1 receptor agonist therapy is linked to a small but statistically significant decrease in hepatic steatosis in patients with NAFLD when it is evaluated in various ways. These results indicate the clinical potential of GLP-1RAs in the treatment of NAFLD. To validate these effects, larger, more protracted randomized studies, with standardized steatosis outcomes are needed to understand their effects on the progression of the disease and the clinical outcomes