A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D)

Abstract

Treatment options for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), two conditions which coexist, are limited though weight loss is an important strategy to improve outcomes in either disease. Glucagon-like peptide 1 receptor agonist (GLP1-RA) present a novel option to treat this dual disease by their salutary effects on glycaemic control and weight reduction. Eight randomized controlled trials on T2D and NAFLD from the Cochrane Library, Embase, and PubMed were included in this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size. In a pooled population of 615 patients—297 on GLP1-RA and 318 in the control arm, GLP1-RA produced a significant improvement in alanine aminotransferase [standardised mean difference (SDM), − 0.56, 95% CI − 0.88 to − 0.25, P < 0.01], aspartate aminotransferase (SDM, − 0.44, SE, 95% CI − 0.64 to − 0.24, P < 0.01), gamma glutaryl transaminase (SDM, − 0.60, 95% CI − 0.86 to − 0.34, P < 0.01) and reduction in liver fat content (LFC) (SDM, − 0.43, 95% CI − 0.74 to − 0.12, P < 0.01), as well as glycosylated haemoglobin (SDM, − 0.40, 95% CI, − 0.61 to − 0.19, P < 0.01) and weight (SDM, − 0.66, 95% CI, − 0.88 to − 0.44, P < 0.01), in comparison to standard of care or placebo. Significant improvement in biopsy resolution was also seen in the GLP1-RA arm (Rate Ratio, 6.60, 95% CI 2.67 to 16.29, P < 0.01). This is possibly the first meta-analysis conducted exclusively in patients with T2D and NAFLD which presents a strong signal that GLP1-RA, improve liver function and histology by improving glycaemia, reducing body weight and hepatic fat, which in turn reduces hepatic inflammation. Trial Registration: PROSPERO (ID: CRD42021228824).