S2661 SGLT2 Inhibitors Improve Liver Enzyme and Fat Content Patients With MASLD and Type 2 Diabetes: Results of a Meta-Analysis of Randomized Control Trials

Introduction: MASLD (metabolic dysfunction–associated steatotic liver disease) is highly prevalent in individuals with type 2 diabetes (T2DM) and is linked to increased risks of cirrhosis and cardiovascular disease. SGLT2 inhibitors are antidiabetic agents with metabolic effects that may also improve hepatic outcomes. We performed a meta-analysis to assess the impact of SGLT2 inhibitors on liver enzymes and imaging-based hepatic steatosis in patients with MASLD and T2DM. Methods: We carried out a systematic search of PubMed, Embase, and Web of Science to identify randomized controlled trials in adults with MASLD and T2DM comparing SGLT2 inhibitors with placebo or active controls. Outcomes of interest included changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic steatosis as measured by MRI-PDFF, FibroScan, ultrasound, or CT. Studies were included if both baseline and post-treatment values were reported. Results: Six RCTs (441 patients) were included; 231 received an SGLT2 inhibitor and 210 received a placebo or active comparator (pioglitazone, sitagliptin, teneligliptin). SGLT2 inhibitors led to significant reductions in AST (mean difference −8.0 U/L, 95% CI −14.3 to −1.7, P = 0.014) and ALT (−11.3 U/L, 95% CI −20.6 to −2.0, P = 0.018). All studies reported liver imaging outcomes, with 5 demonstrating greater reductions in liver fat with SGLT2 therapy. Improvements were seen across MRI-PDFF, FibroScan CAP, ultrasound grading, and CT attenuation. In one study, intrahepatic lipid decreased by 5.2% with empagliflozin vs 1.9% with sitagliptin (P = 0.044). Another showed a −29 dB/m CAP reduction vs −16 with placebo (P = 0.05). Conclusion: SGLT2 inhibitors significantly improve ALT, AST, and liver fat content in patients with MASLD and T2DM. Improvements were observed across multiple imaging modalities and agents. These findings further support the role of SGLT2 inhibitors in managing hepatic outcomes in MASLD.