Abstract
Aims This meta-analysis of randomized placebo-controlled clinical trials assessed the effect of glucose-like peptide-1-receptor agonists (GLP-1RA) on the lipid profile and liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods Randomized placebo-controlled trials investigating GLP-1RA on the lipid profile and liver enzymes in patients with NAFLD were searched in PubMed-Medline, Scopus, Web of Science, and Google Scholar databases (from inception to January 2020). A random-effects model and a generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted. Weighted random-effects meta-regression was performed on potential confounders on lipid profile and liver enzyme concentrations. Results 12 studies were identified (12 GLP-1RA arms; 677 subjects) that showed treatment with GLP-1RA reduced alanine transaminase (ALT) concentrations (WMD = −10.14, 95%CI = [−15.84, −0.44], P < 0.001), gamma-glutamyl transferase (GGT) (WMD = −11.53, 95%CI = [−15.21,−7.85], P < 0.001), and alaline phosphatase (ALP) (WMD = −8.29, 95%CI = [−11.34, −5.24], P < 0.001). Aspartate aminotransferase (AST) (WMD = −2.95, 95% CI = [−7.26, 1.37], P=0.18) was unchanged. GLP-1 therapy did not alter triglycerides (TC) (WMD = −7.07, 95%CI = [−17.51, 3.37], P=0.18), total cholesterol (TC) (WMD = −1.17 (−5.25, 2.91), P=0.57), high-density lipoprotein (HDL-C) (WMD = 0.97, 95%CI = [−1.63, 3.58], P=0.46), or low-density lipoprotein (LDL-C) (WMD = −1.67, 95%CI = [−10.08, 6.74], P=0.69) in comparison with controls. Conclusion The results of this meta-analysis suggest that GLP-1RA treatment significantly reduces liver enzymes in patients with NAFLD, but the lipid profile is unaffected.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is an increasing global public health problem with a worldwide prevalence of NAFLD estimated at approximately 25% [1] and a common cause of chronic liver disease [2], and it is predicted to develop in more than 30% of the US adult population [3]
12 studies were identified (12 Glucagon-like peptide-1 receptor agonists (GLP-1RA) arms; 677 subjects) that showed treatment with GLP1RA reduced alanine transaminase (ALT) concentrations (WMD − 10.14, 95%confidence interval (CI) [− 15.84, − 0.44], P < 0.001), gamma-glutamyl transferase (GGT) (WMD − 11.53, 95%CI [− 15.21,− 7.85], P < 0.001), and alaline phosphatase (ALP) (WMD − 8.29, 95%CI [− 11.34, − 5.24], P < 0.001)
Search Strategy. is meta-analysis was conducted according to PRISMA instruction of systematic reviews and meta-analysis [21]. e scientific web-portals such as PubMed, Scopus, Cochrane, Web of Science, Embase, and Scholar were carefully surveyed to extract all relevant literature on the effects of GLP-1 receptor agonists on lipid profile and liver enzymes in patients with nonalcoholic fatty liver disease published until January 2020. e key terms that were applied to finalize the first step of the search strategy to gather target data are shown in Appendix
Summary
Nonalcoholic fatty liver disease (NAFLD) is an increasing global public health problem with a worldwide prevalence of NAFLD estimated at approximately 25% [1] and a common cause of chronic liver disease [2], and it is predicted to develop in more than 30% of the US adult population [3]. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a newly introduced class of antidiabetic drugs that improve glycemic control via several molecular pathways [7, 8]. Ere is an association between NAFLD and metabolic syndrome that causes DM, dyslipidemia, and obesity suggesting that breaking this cycle by GLP-1 agonists may have therapeutic potential [18], as they may have anti-inflammation activity [19]. Erefore, GLP-1 receptor analogue therapy may have the potential for the treatment of NAFLD and NASH patients; it is unclear from the studies that have been done whether GLP-1 agonists improve the hepatic enzyme and lipid profiles in subjects with NAFLD; this systematic review and meta-analysis were undertaken GLP-1RAs have other beneficial effects [9,10,11,12,13,14,15,16] and decrease energy intake and body weight by prolonging gastric emptying and inducing satiety [17]. ere is an association between NAFLD and metabolic syndrome that causes DM, dyslipidemia, and obesity suggesting that breaking this cycle by GLP-1 agonists may have therapeutic potential [18], as they may have anti-inflammation activity [19]. e administration of the GLP-1RA liraglutide was suggested to directly reduce liver fibrosis and steatosis in an in vivo study [17] and reduces markers of fibrosis in man [20]. erefore, GLP-1 receptor analogue therapy may have the potential for the treatment of NAFLD and NASH patients; it is unclear from the studies that have been done whether GLP-1 agonists improve the hepatic enzyme and lipid profiles in subjects with NAFLD; this systematic review and meta-analysis were undertaken
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