Eleni A. Karavia, Andreas Pittaras, Ourania Andreopoulou, Aikaterini Hatziri, Amalia Makrydimitri, Dimitrios Anagnostopoulos, Patroklos Vareltzis, Kyriakos E. Kypreos
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic dysfunction-associated steatotic liver disease (MASLD), represents a growing global health burden closely linked to obesity, insulin resistance, and dietary patterns. Despite intense drug-development efforts, effective and widely approved pharmacological therapies remain limited. Methods: In this work, we systematically evaluated the quality of clinical evidence supporting currently proposed pharmacological treatments for MASLD/MASLD using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, focusing on phase III and IV clinical trials. Results: Our analysis demonstrates that overall quality of evidence for most pharmacological agents ranges from very low to moderate, primarily due to imprecision and suspected publication bias. Conclusions: Overall, our findings reinforce that, in the current therapeutic landscape, pharmacological therapies should be reserved for carefully selected patients and interpreted in the context of limited evidence certainty.