Semaglutide and Its Potential Hepatoprotective Effects Against Acute Drug-Induced Liver Injury

Drug-induced liver injury (DILI) is hepatic damage caused by medications, illegal drugs, herbal products, or dietary supplements and is related to inflammation, oxidative stress, and mitochondrial dysfunction. Manifestations can vary from isolated liver enzyme elevation to fulminant hepatic failure. As many well-established therapeutic options do not exist, it is crucial to explore new hepatoprotective agents. Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA), primarily used as an antidiabetic and anti-obesity agent, which manifests pleiotropic effects through activation of GLP-1 receptors. Recently, the Food and Drug Administration officially approved semaglutide for the treatment of metabolic dysfunction-associated steatohepatitis in adults with moderate-to-advanced fibrosis. The European Medicines Agency has issued a positive recommendation on the same indication. Proposed mechanisms for semaglutide's liver beneficial effects include anti-inflammatory, antioxidant, and anti-apoptotic actions, as well as improved microcirculation, reduced lipotoxicity, and enhanced hepatic regeneration. Preclinical studies in models of toxic and ischemic liver injury demonstrate that GLP-1 RAs reduce hepatic damage. Semaglutide may offer therapeutic benefits in DILI, either as supportive treatment or as a stabilizing agent prior to transplantation. Still, further preclinical studies are required to provide the essential frame for clinical investigations in this setting.