Pharmacotherapy for MASLD: current evidence and challenges in clinical practice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by a complex pathophysiology driven by intertwined metabolic and hepatic pathways, enabling the identification of multiple therapeutic targets and a rapidly expanding drug development pipeline. This review summarizes the current and emerging therapeutic landscape for MASLD and discusses key challenges for clinical implementation. The imminent availability of several new therapies is expected to pose important clinical challenges, particularly in accurately identifying patients most likely to benefit. Currently, resmetirom and semaglutide are the only two drugs conditionally approved for patients with fibrosis stages 2-3, pending final phase 3 outcomes, and represent the main liver-directed and metabolic-focused therapeutic strategies, respectively. Treatment selection should follow a phenotype-based approach integrating metabolic profile and liver disease stage. Non-invasive tests are central for assessing treatment eligibility; however, strategies incorporating metabolic risk profiling and longitudinal monitoring will be essential to optimize real-world management of MASH.