Is There a Role for GLP-1RAs in NAFLD Management?

Liver cirrhosis
Liver cirrhosis
Investigators conducted a review to assess the role of glucagon-like peptide-1 receptor agonists in the treatment of NAFLD and NASH.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide and liraglutide may hold potential in the management of nonalcoholic fatty liver disease (NAFLD), given their observed effects on steatohepatitis, according to literature review findings published in the Journal of Clinical Endocrinology and Metabolism.

The researchers sought to synthesize evidence from published observational studies, randomized controlled trials, and meta-analyses that reported on the use of GLP-1RAs in NAFLD. According to the investigators, guidelines recommend the use of GLP-1RAs for weight and glycemic management in patients with type 2 diabetes. The researchers note that previous studies show an association between GLP-1RA use in patients with diabetes and cardiovascular risk reduction; these findings come “as a valuable reassurance for their use” in those with NAFLD, considering cardiovascular disease is a leading cause of death in this population.

While the researchers note that the hepatic effects of GLP-1RAs involve adaptation of portal and peripheral insulin and glucagon levels and improvements in hepatocyte mitochondrial function, they explained that the hepatic effects of these agents do “not appear to be from a direct effect on hepatocytes as the most recent evidence suggests that hepatocytes lack GLP-1 receptors.”

The researchers point to liraglutide as the most broadly studied GLP-1RA in NAFLD. These studies have shown an association between the use of this agent and reductions in weight and plasma aminotransferases, as well as decreases in liver fat content and improvements in hemoglobin A1c and insulin secretion.

Additionally, the researchers note that dulaglutide has been shown to reduce plasma aminotransferases in patients with type 2 diabetes, a reduction consistent with patterns seen in steatosis reduction. The researchers also cited additional studies reporting a potential benefit with once daily semaglutide on steatohepatitis and hepatic fibrosis.

The researchers concluded that future studies are needed to further assess the role of oral GLP-1RAs, sodium-glucose cotransporter-2 inhibitors, and a combination of diabetes medications in NAFLD. “It is likely that in the near future GLP-1RA will play a greater role among clinicians to treat patients with NAFLD,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Patel Chavez C, Cusi K, Kadiyala S. The emerging role of glucagon-like peptide-1 receptor agonists for the management of NAFLD. J Clin Endocrinol Metab. Published online August 18, 2021. doi:10.1210/clinem/dgab578