Pharmacological treatment of steatotic liver disease associated with metabolic dysfunction

The treatment of metabolic dysfunction associated steatotic liver disease (MASLD) can be classified into two broad categories: pharmacologic and non-pharmacologic. The latter is based on the adoption of sustained lifestyle changes. Weight loss is the cornerstone of MASLD management; however, fewer than 10% of patients achieve this goal in a sustained manner within one year. Pharmacologic treatment for MASLD should be considered in patients with clinically significant liver disease or at high risk of progression, particularly when lifestyle interventions fail to meet therapeutic targets. Among the agents with the strongest evidence are vitamin E for non-diabetic patients with metabolic dysfunction associated steatohepatitis, and pioglitazone for individuals with or without type 2 diabetes—both with demonstrated efficacy in improving steatohepatitis. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1 and glucose-dependent insulinotropic peptide (GIP) agonists provide additional benefits by inducing significant weight loss and improving the cardiometabolic profile, with consistent data showing histologic improvement. Sodium glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin and dapagliflozin, and peroxisome proliferator-activated receptors (PPAR) agonists, such as lanifibranor, show favorable effects on steatosis and inflammation, although evidence for their impact on fibrosis is more limited. Resmetirom, for its part, substantially reduces hepatic fat and has demonstrated histologic improvement.