The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD

Abstract

Context The burden of cirrhosis from NAFLD is reaching epidemic proportions in the United States. This calls for greater awareness among endocrinologists, who often see but may miss the diagnosis in adults with obesity or type 2 diabetes mellitus (T2D) who are at the highest risk. At the same time, recent studies suggest that GLP-1RAs are beneficial versus steatohepatitis (NASH) in this population. This minireview aims to assist endocrinologists to recognize the condition and recent work on the role of GLP-1RAs in NAFLD/NASH. Evidence acquisition Evidence from observational studies, randomized controlled trials, and meta-analyses. Evidence Synthesis Endocrinologists should lead multidisciplinary teams to implement recent consensus statements on NAFLD that call for screening and treatment of clinically significant fibrosis to prevent cirrhosis, especially in the high-risk groups (i.e., people with obesity, prediabetes or T2D). With no FDA-approved agents, weight loss is central to their successful management, with pharmacological treatment options limited today to vitamin E (in people without T2D) and diabetes medications that reverse steatohepatitis, such as pioglitazone or GLP-1RA. Recently the benefit of GLP-1RAs in NAFLD, suggested from earlier trials, has been confirmed in adults with biopsy-proven NASH. In 2021, the FDA also approved semaglutide for obesity management. Conclusion A paradigm change is developing between the endocrinologist’s greater awareness about their critical role to curve the epidemic of NAFLD and new clinical care pathways that include a broader use of GLP-1RAs in the management of these complex patients.

Non‐alcoholic fatty liver disease and type 2 diabetes: An update

“…As GLP1 receptors are not present in the hepatocytes, it is generally agreed that GLP1 receptor agonists exert these beneficial effects indirectly through weight loss with alleviation of adipose tissue dysfunction and lipotoxicity, modulation of portal and peripheral plasma insulin and glucagon levels, as well as improvement in hepatocyte mitochondrial function and hepatic insulin resistance 89 .…”

Association between use of liraglutide and liver fibrosis in patients with type 2 diabetes

“…In recent years, the role of GLP-1RAs in NAFLD has also been investigated. The role of GLP-1RAs in hepatic steatosis and NASH is demonstrated in the previous studies ( 15 , 16 , 18 ). In contrast, its role in liver fibrosis in NAFLD is still controversial.…”

“…They are also effective in reducing both body weight and visceral adipose tissue, and have beneficial effects on the risk of cardiovascular and renal outcomes ( 9 – 13 ). In addition, recent evidence has shown that GLP-1RAs also improve hepatic histological components of NAFLD ( 14 – 16 ). Liraglutide and semaglutide consistently resolved NASH histologically in 40% to 60% of patients ( 17 , 18 ).…”

Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review

“…Reports suggest that patients with NASH have impaired GLP-1 secretion ( 69 ); it strengthens the proposition of GLP-1 receptor agonists as a therapeutic option for management of NASH. Various GLP-1 receptor agonists like liraglutide, dulaglutide, semaglutide have shown to improve the pathogenesis of NASH ( 70 ). Tirzepatide, a dual agonist of GLP-1 and GIP has been found to improve various NASH-biomarkers in patients with type 2 diabetes ( 71 ).…”