[New Therapeutic Approaches for MASH: Mechanisms and Clinical Promise]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder characterized by inflammation, fibrosis, and metabolic dysfunction. In recent years, therapeutic options have expanded significantly. The thyroid hormone receptor-β agonist resmetirom became the first drug approved in Germany in 2025 for non-cirrhotic MASH with moderate to advanced fibrosis. Furthermore, incretin mimetics, originally developed for diabetes and obesity, are being investigated. In a phase 3 study, semaglutide demonstrated significant improvements in hepatic inflammation and fibrosis. Beyond GLP-1 analogs, which act indirectly through metabolic pathways, several liver fibrosis-specific therapies are emerging, including FGF-21 analogs and dual incretin receptor agonists (e.g. survodutide) that directly affect hepatocytes via glucagon receptor signaling. Combination therapies are increasingly being explored to harness synergistic effects and enable individualized treatment. Ongoing phase 3 studies assess long-term efficacy and safety. In parallel, biomarkers are being refined for patient selection and treatment monitoring. The German SLD Registry will collect patient data and clinical outcomes following the implementation of new therapies. This review summarizes recent advances and future perspectives in the pharmacological treatment of MASH. The combination of metabolic and liver-targeted therapies offers substantial promise for personalized medicine.