Pharmacological Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease in a New Era for Obesity and Metabolic Medicine: A State-of-the-Art Review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and a major cause of cirrhosis, hepatocellular carcinoma, and liver-related mortality. Weight loss via positive health behavioral changes is the cornerstone of management of MASLD. However, this is a huge challenge for many patients, highlighting the need for effective pharmacological therapies. Two pharmacological agents have received accelerated approval for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), the progressive inflammatory form of MASLD, namely resmetirom, an oral, liver-directed, selective thyroid hormone receptor-β agonist, and semaglutide, a glucagon-like peptide-1 receptor agonist. Despite recent advances, effective pharmacological therapy for MASH-related cirrhosis remains an unmet need, underscoring the importance of early identification and intervention. This narrative review summarizes the current pharmacological therapy landscape of MASLD, including emerging incretin-based therapies and fibroblast growth factor-21 analogues, as well as current guidance on the use of non-invasive tests for treatment selection and monitoring for treatment response. It also provides a background on recent advances in obesity and metabolic medicine, highlighting the evolving paradigm of complication-centric obesity management and the potential role of incretin-based therapies as the backbone of the management of obesity and obesity-related conditions, including MASLD.