Anti-obesity medications, the new frontiers in metabolic dysfunction-associated fatty liver disease: Efficacy, limitations, and future directions

Figure 1 Historical evolution of anti-obesity pharmacotherapy and its application in metabolic associated steatotic liver disease and metabolic dysfunction-associated fatty liver disease. Early agents such as orlistat and centrally acting drugs showed limited hepatic benefit. The introduction of incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists, marked a paradigm shift with demonstrated improvements in liver fat and histologic resolution of steatohepatitis. Dual and triple incretin agonists show promising metabolic effects, although metabolic associated steatotic liver disease-specific histologic outcomes remain under investigation. MASLD: Metabolic associated steatotic liver disease; GLP-1: Glucagon-like peptide-1; GIP: Glucose-dependent insulinotropic polypeptide; CNS: Central nervous system; MAFLD: Metabolic dysfunction-associated fatty liver disease; RCT: Randomized controlled trial; NASH: Non-alcoholic steatohepatitis; MRI: Magnetic resonance imaging; PDFF: Proton density fat fraction.

Figure 2 Challenges and obstacles to the use of anti-obesity medications in metabolic dysfunction-associated fatty liver disease and metabolic associated steatotic liver disease. MAFLD: Metabolic dysfunction-associated fatty liver disease; MASLD: Metabolic associated steatotic liver disease; HCC: Hepatocellular carcinoma.