Background <p>Metabolic dysfunction-associated steatotic liver disease (MASLD), closely associated with type 2 diabetes mellitus (T2DM), is a rising global health concern.</p> Objective <p>With insulin resistance and hepatic inflammation at its core, MASLD contributes significantly to the development of liver fibrosis and eventual cirrhosis.</p> Methods <p>This twin-centre prospective study aimed to assess the long-term effects of oral Semaglutide on hepatic and metabolic parameters in patients with T2DM. A total of 196 patients received oral Semaglutide for 18 months, and changes in liver enzymes, HbA1c, Fibro Scan-derived parameters (CAP and liver stiffness), and Fibrosis-4 index (Fib-4) were evaluated at baseline and after 18 months of treatment. Blood glucose was assessed using venous plasma samples analysed by the hexokinase enzymatic method.</p> Results <p>Demonstrated statistically significant reductions in SGOT, SGPT, GGT, HbA1c, CAP, liver stiffness, and Fib-4 scores. These findings underscore the hepatoprotective and antifibrotic potential of Semaglutide in patients with coexisting T2DM and MASLD, although the absence of histological confirmation and a comparator group remain limitations.</p> Conclusion <p>These findings underscore the hepatoprotective and antifibrotic potential of Semaglutide in patients with coexisting T2DM and MASLD, although the absence of histological confirmation and a comparator group remain limitations.</p>