Advances in the Pharmacologic Management of MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its inflammatory subtype metabolic dysfunction-associated steatohepatitis (MASH) are now the most common types of chronic liver disease worldwide and major contributors to cirrhosis, hepatocellular carcinoma, and liver transplantation. The disease develops from systemic metabolic dysfunction, including obesity, insulin resistance, and dyslipidemia. These factors increase hepatic fatty acid influx and de novo lipogenesis, driving steatosis, inflammation, and progressive fibrosis. Lifestyle modification is the foundation of treatment. Even modest weight loss can improve steatosis and inflammatory activity, although long-term adherence is often limited. These challenges have accelerated interest in targeted pharmacologic therapy. Thyroid hormone receptor beta agonists such as resmetirom reduce hepatic fat, improve lipid parameters, and show histologic benefit. Peroxisome proliferator activated receptor (PPAR) agents have progressed from single isoform approaches to pan-PPAR activation. Lanifibranor has demonstrated dose-dependent improvements in steatosis, activity, and fibrosis and has achieved key regulatory endpoints. Additional metabolic therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), offer complementary benefits for weight, insulin sensitivity, and liver inflammation. These emerging options represent a promising shift toward disease modifying treatment for MASLD.