Comparative efficacy of SGLT2 Inhibitors and Obeticholic Acid in MAFLD and Fibrosis: A Systematic Review

Background Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD) is a metabolic liver disorder characterised by excessive fat buildup in the liver, closely linked with obesity, diabetes, and lifestyle factors, with potential progression into advanced liver disease. This review aims to evaluate the therapeutic role of Sodium–glucose cotransporter 2 inhibitors (SGLT2i) and Obeticholic acid (OCA) in MAFLD-related fibrosis. Recently, the Food and Drug Administration (FDA) approved Resmetirom and Semaglutide for Metabolic dysfunction-Associated Steatohepatitis (MASH) with moderate to advanced fibrosis. OCA is currently under research for its efficacy in treating MASH. At the same time, SGLT2i are being investigated in various phases for MAFLD, though large-scale Phase III trials are still forthcoming. Methods A systematic review was conducted, identifying a total of 5,253 articles from PubMed, Embase, Google Scholar and Web of Science. Only peer-reviewed, full-text RCTs were included and assessed for bias using RoB 2. After a strict quality assessment, data from 16 studies were gathered and included. The certainty of Evidence was evaluated for every outcome using the GRADE approach. Results Both OCA and SGLT2i lead to histological improvement and improve liver enzyme levels. However, MASH resolution was more prominent with OCA, though it was attributed to adverse effects such as dyslipidemia and pruritus. Conclusion Despite the potential of both drug classes, this parallel evidence synthesis emphasises the necessity of additional research to determine their relative safety and efficacy in MAFLD.