Background <p>As the prevalence of metabolic dysfunction-associated steatohepatitis (MASH) continues to rise, drug development has accelerated, with growing interest in therapeutic strategies that harness metabolic hormones. Metabolic hormone-based approaches, particularly those originally developed for obesity and diabetes, have shown potential to mitigate MASH. Notably, the glucagon-like peptide-1 receptor (GLP-1R) agonist semaglutide received accelerated approval for MASH in 2025. In addition, GLP-1R-based multi-agonists and candidates leveraging the metabolic actions of fibroblast growth factor (FGF) 21 are in active clinical development for liver disease.</p> Area covered <p>This review provides an overview of metabolic hormone-based therapies, including incretin-based drugs and FGF analogs, that are currently under clinical development for MASH. It also discusses liver-targeting strategies to achieve selective hepatic delivery, which may vary according to the expression of liver-specific receptors and fibrosis degree.</p> Expert opinion <p>Within the MASH therapeutic landscape, incretin-based therapies are evolving from GLP-1R mono-agonist to multi-agonist approaches that aim to combine weight loss-mediated benefits with mechanisms that directly modulate hepatic lipid handling and inflammation. Moreover, the therapeutic actions of metabolic hormones in MASH, together with the expression profiles of their corresponding receptors, play a critical role in determining targeting strategies. Stage-specific and liver-selective delivery strategies will likely distinguish next-generation candidates. This review summarizes the pharmacological mechanisms and delivery strategies of each agent class and further explores these receptors as potential targets to inform the development of precision therapeutic approaches.</p>