Drug treatment of MASH from none to (too) many options?

The management of metabolic dysfunction-associated steatohepatitis (MASH) has evolved significantly, transitioning from a lack of therapeutic options to resmetiroma and semaglutide being licensed for use in MASH. With this evolving backdrop, this perspective article aims to explore the biological and clinical activities of tirzepatide, denifanstat, semaglutide, dapagliflozin, and efruxifermin, for which robust evidence of activity has been published. Tirzepatide and semaglutide, both GLP-1 receptor agonists, have shown significant efficacy in weight loss and metabolic improvements, while dapagliflozin, an SGLT2 inhibitor, offers renal protection alongside metabolic benefits. Denifanstat represents a novel approach targeting inflammation in MASH, potentially addressing the underlying pathophysiology. Efruxifermin is emerging as an innovative agent with dual mechanisms aimed at liver health and metabolic regulation. As we navigate this landscape of therapeutic options, we will discuss the implications for clinical practice and the necessity for personalized treatment strategies in managing MASH effectively. The rapid development of these therapies prompts critical evaluation—are we moving towards optimal treatment paradigms or encountering the challenge of over-treatment? This article seeks to provide insights into these evolving dynamics in MASH management.