Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Metabolic Associated Fatty Liver Disease

Abstract

Background: Clinical trials examining the therapeutic benefits of glucagon-like peptide-1 receptor agonists (GLP-1RA) on patients with metabolic associated fatty liver disease (MAFLD) have reported inconsistent results. The aim of this meta-analysis was to verify the role of GLP-1RA in the treatment of MAFLD patients. Materials and Methods:We searched PubMed, Embase, Medline, and the Cochrane Library for randomized controlled trials published that compared GLP-1RA with the control treatment in patients with MAFLD till to July 30, 2020. The effects of GLP-1RA on liver histology, body mass index, waist circumference (WC), aspartate aminotransferase, total cholesterol, triglycerides (TG), low-density lipoprotein and high-density lipoprotein were evaluated.Results: Thirteen trials involving 704 patients were included in the meta-analysis. Compared with the control treatment, GLP-1RA treatment induced a greater resolution of steatohepatitis [RR = 2.87; 95% confidence interval (CI): 0.89 to 9.23], delayed the progression of liver fibrosis (RR = 3.83, 95% CI: 0.91 to 16.07) and reduced liver fat deposition (MD: −1.40; 95% CI: −2.75 to −0.05). In addition, it reduced the body mass index (MD: −1.15; 95% CI: −2.26 to −0.04), WC (MD: −3.33; 95% CI: −6.31 to −0.35) and improved serum aspartate aminotransferase (MD: −3.04; 95% CI: −5.93 to −0.16) and total cholesterol (MD: −0.20; 95% CI: −0.28 to −0.13).Conclusion: GLP-1RA improves liver steatosis and fibrosis. It is also beneficial to metabolic syndrome as it reduces BMI, WC, and hyperlipidemia.

Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism

“…In addition, Sharma et al [64] studied GLP-1 and receptors on hepatocytes and found that the combination of them can reduce the lipid stress response in hepatocytes, reduce the lipid load of hepatocytes, delay steatosis, and ultimately prevent NAFLD. Several other studies have also provided evidence that GLP-1RA can reduce hepatic fat accumulation and reduce steatosis in liver tissue by regulating the expression of genes and proteins related to the fat synthesis pathway [109,110]. However, there are no targeted drugs specifically designed to treat NAFLD.…”

Interplay between metabolic dysfunction-associated fatty liver disease and chronic kidney disease: Epidemiology, pathophysiologic mechanisms, and treatment considerations

“…Moreover, in a meta-analysis of 4 randomized clinical trials, semaglutide was associated with significant decreases in body weight, alanine aminotransferase, liver steatosis, and stiffness[ 98 ]. GLP1-RAs may also improve histologic features on MAFLD, such as liver fat deposition, steatohepatitis, and fibrosis, as shown by the systematic review and meta-analysis of Jianping et al [ 72 ].…”

The Role of GLP1-RAs in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using In Vitro Models of NAFLD

“…In addition, despite the significant amount of research focused on the role of GLP-1 receptors in glucose metabolism and insulin secretion, there is a relative scarcity of comprehensive reviews synthesizing the effects of GLP-1RAs specifically on hepatic lipid metabolism in NAFLD. A significant number of studies have investigated this topic [ 32 , 40 , 41 , 42 , 43 ]. However, the aim of this article is to provide a more comprehensive review of recently obtained knowledge regarding specifically underlying molecular and cellular mechanisms of GLP1 effects on hepatic lipid metabolism and its potential in the treatment of NAFLD.…”