GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives

Abstract

To date, non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease, affecting up to 70% of patients with diabetes. Currently, there are no specific drugs available for its treatment. Beyond their anti-hyperglycemic effect and the surprising role of cardio- and nephroprotection, GLP-1 receptor agonists (GLP-1 RAs) have shown a significant impact on body weight and clinical, biochemical and histological markers of fatty liver and fibrosis in patients with NAFLD. Therefore, GLP-1 RAs could be a weapon for the treatment of both diabetes mellitus and NAFLD. The aim of this review is to summarize the evidence currently available on the role of GLP-1 RAs in the treatment of NAFLD and to hypothesize potential future scenarios.

Liraglutide ameliorates hepatic steatosis via retinoic acid receptor‐related orphan receptor α‐mediated autophagy pathway

“…Liraglutide is a commonly used GLP-1 receptor agonist and exhibits potential protective effects on NAFLD. 19 However, benefits of liraglutide on hepatic steatosis have not been well established. A 48-week intervention of liraglutide attenuates steatosis and improves histological resolution of steatohepatitis in patients with NAFLD, 20 while a 12-week liraglutide treatment does not change hepatic steatosis or fibrosis in type 2 diabetic patients in randomized controlled trials.…”

“…Although not fully clarified, mechanisms underlying the action of liraglutide on hepatic steatosis may be multifactorial. 19 RORα is a ligand-dependent transcription factor that regulates the expression of various genes involved in lipid metabolism, which could potentially prevent the progression of NAFLD. 8,34 However, the exact influence of liraglutide on RORα-mediated hepatic steatosis has not been studied previously.…”

“…Liraglutide is a commonly used GLP‐1 receptor agonist and exhibits potential protective effects on NAFLD 19 . However, benefits of liraglutide on hepatic steatosis have not been well established.…”

Effects of once‐weekly glucagon‐like peptide‐1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin‐angiotensin system

“…Besides, GLP‐1 RA are also present in the lipid microregions of steatotic hepatocytes, 67 which can reduce the production of adipose tissue (such as TGs and LDL) and alleviate the metabolic burden caused by ectopic fat accumulation in the liver 68,69 . Use of the GLP‐1 RA has been proven to be an effective method of treatment for improving non‐alcoholic fatty liver disease because of their significant weight loss effect 70 …”

“…68,69 Use of the GLP-1 RA has been proven to be an effective method of treatment for improving non-alcoholic fatty liver disease because of their significant weight loss effect. 70 Although great efforts were made to obtain the final results, the study has some limitations. The primary focus of this study was the effect of once-weekly GLP-1 RA on cardiovascular events, and the primary outcome was MACE.…”