Glucagon-Like Peptide-1 Receptor Agonists for Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: A Meta-Analysis

Abstract

ObjectiveNon-alcoholic fatty liver disease is highly prevalent in patients with type 2 diabetes mellitus. Studies on glucagon-like peptide-1 receptor agonists for the treatment of non-alcoholic fatty liver disease have reported promising results. Despite this, there has been limited evidence of its efficacy in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus. This meta-analysis examined existing evidence on the efficacy of glucagon-like peptide-1 receptor agonists on the management of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus.MethodsMedline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles discussing the efficacy of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Values of standardized mean differences (SMD) and risk ratio (RR) were determined for continuous outcomes and dichotomous outcomes respectively.Results8 studies involving 1,454 patients from 5 randomized controlled trials and 3 cohort studies were included in the analysis. Our analysis found significant improvements in hepatic fat content, liver biochemistry, body composition, glucose parameters, lipid parameters, insulin sensitivity and inflammatory markers following glucagon-like peptide-1 receptor agonist treatment. Glucagon-like peptide-1 receptor agonists significantly decreased hepatic fat content compared to metformin and insulin-based therapies. Glucagon-like peptide-1 receptor agonists also improved fibrosis markers, but this did not reach statistical significance.ConclusionWith a high prevalence of obesity and non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonist treatment shows promise in improving both diabetes and non-alcoholic fatty liver disease phenotype.

Meta‐analysis: analysis of mechanistic pathways in the treatment of non‐alcoholic steatohepatitis. Evidence from a Bayesian network meta‐analysis

“…Diabetes has been known to influence the progression on NASH or potentially alter treatment outcomes 73 . However, a sensitivity analysis of diabetes only patients was deemed inappropriate due to the lack of granularity in reporting and diabetes only trials have only been conducted in the context of NAFLD 74‐76 . Additionally, the proposed classification in the analysis was built on the consensus of NASH trials but may not account for unique properties of individual class effect.…”

“…Additionally, the proposed classification in the analysis was built on the consensus of NASH trials but may not account for unique properties of individual class effect. For instance, glucagon‐like peptide 1 receptor antagonist (GLP1‐RA) can result in weight loss that can indirectly affect liver histology 74,77 . A ≥ 5% reduction of weight can result in resolution of NASH and fibrosis improvement but a network meta regression to account for a ≥ 5% of weight reduction was deemed inappropriate due to the lack of reporting 66 .…”

A clinical overview of non‐alcoholic fatty liver disease: A guide to diagnosis, the clinical features, and complications—What the non‐specialist needs to know

“…106 While both these drug classes have not demonstrated definitive proof of benefit in patients with NAFLD, recent meta-analysis performed have demonstrated improvement in liver steatosis and metabolic markers in diabetic patients with NAFLD on both these agents. 107,108 The bulk of patients managed by the primary care physician would not have significant fibrosis; thus, placed at greater risk of cardiovascular events and other associations of NAFLD as compared to liver-related events. As such, it may make sense to preferentially use these agents in diabetic patients with NAFLD, especially in those with earlier stages of the disease.…”

Current Options and Future Directions for NAFLD and NASH Treatment

“…GLP-1 receptor agonists can inhibit hepatic fat accumulation as the effect of metformin and insulin-based treatment [ 125 ]. In addition, they can moderately improve liver fibrosis.…”