Prospects for Use of Incretin Mimetics in Metabolically Associated Fatty Liver Disease

Abstract

Aim. To review current data on the effect of incretin mimetics on the course of metabolically associated fatty liver disease. Key points. In obesity, the liver is exposed to the negative effects of excessive lipid accumulation. This process underlies metabolically associated liver disease (MAFLD), a condition that entails carbohydrate and lipid metabolism disorders and increases the risk of adverse cardiovascular events. The basis of MAFLD treatment is weight loss. The most effective class of drugs for weight loss are currently considered to be drugs from the incretin mimetics group. Data on the effect of incretin mimetics on the course of MAFLD are currently quite scattered and sparse due to the complexity and invasiveness of the histological research method. Incretin hormones (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide), as well as glucagon, are actively involved in metabolic processes affected in the pathogenesis of MAFLD, but the degree of their synergism and antagonism at the liver level continues to be studied. In connection with the emergence of new molecules that have the ability to act on the receptors of the above hormones, it seems relevant to evaluate their effect on the course of MAFLD. Conclusion. Modern incretin drugs affect many components of the metabolic syndrome: GLP-1 agonists affect eating behavior and glycemia, have the ability to reduce the severity of the inflammatory response in adipose tissue, and have a beneficial effect on the lipid profile. The above studies have demonstrated an improvement in morphological parameters in patients with steatosis and steatohepatitis. GLP-1 receptor agonists have not yet been shown to have a significant effect on liver fibrosis, but research in this area is ongoing. Dual GLP-1 and GIP receptor agonists result in greater weight loss, which may theoretically have a more profound effect on the course of MAFLD; results from long-term follow-up and real-world studies are awaited. Preliminary data suggest that dual GLP-1 and glucagon receptor agonists and triple GLP-1, GIP and glucagon receptor agonists may have a direct effect on steatosis and possibly fibrosis. Thus, glucagon receptor targeting may provide additional benefits independent of the degree of weight loss. Keywords: metabolically associated fatty liver disease glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, glucagon