The Effect of Empagliflozin on Non-alcoholic Steatohepatitis and Liver Enzymes Levels in Patients with Type 2 Diabetes Mellitus: A Randomized Clinical Trial

Background: Non-alcoholic steatohepatitis (NASH) is a growing health concern closely linked to insulin resistance, a key factor in the development of type 2 diabetes mellitus (T2DM). Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown to reduce fat mass, improve cardiovascular outcomes, and lower mortality rates. Objectives: This study aimed to evaluate the potential of empagliflozin in reducing liver enzyme levels in patients with T2DM, providing insight into its role in mitigating liver damage associated with NASH. Methods: This was a 24-week, prospective, randomized, placebo-controlled clinical trial conducted at Ayatollah Rouhani Hospital, Babol. A total of 140 eligible patients were randomly assigned to either the placebo or treatment group. The placebo group received standard antidiabetic therapy, while the treatment group received 10 mg of empagliflozin daily in addition to their standard treatment. Data were collected at baseline, and after 12 and 24 weeks. Results: Data from 110 patients were analyzed, with 55 participants in each group. The treatment group showed a significant reduction in aspartate aminotransferase (AST) (P < 0.001), alanine aminotransferase (ALT) (P < 0.001), direct bilirubin (P = 0.001), HDL (P < 0.001), and LDL (P = 0.02) levels. The average fatty liver grade in the treatment group also decreased significantly throughout the trial period (P < 0.001). Changes in AST, ALT, and HDL levels within the treatment group were not affected by age (P < 0.05 in all cases). Aspartate aminotransferase and ALT reductions were significant among females (P < 0.001), as well as in patients with normal or overweight body mass index (BMI): AST (P = 0.002 and P = 0.014, respectively) and ALT (P = 0.001 and P = 0.014, respectively). Conclusions: According to our findings, empagliflozin significantly reduces AST and ALT levels, lowers LDL, increases HDL, and improves fatty liver grading. It may be considered a viable therapeutic option for T2DM patients diagnosed with NASH.