“Efficacy of SGLT2 inhibitors in non-diabetic non-alcoholic fatty liver disease: a systematic review and meta-analysis”

Abstract Background Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is a common chronic liver condition with significant metabolic and cardiovascular implications. Although sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated hepatic benefits in diabetic populations, their role in non-diabetic individuals with NAFLD remains unclear. Objective This meta-analysis aimed to evaluate the effects of SGLT2 inhibitors in non-diabetic NAFLD/MASLD patients. Methods PubMed, Embase, and CENTRAL were searched up to May 2025 for randomized controlled trials (RCTs) comparing SGLT2i with placebo or other pharmacologic agents in non-diabetic adults with NAFLD. Primary outcomes included changes in hepatic function; secondary outcomes assessed anthropometric, metabolic, and imaging-based markers of hepatic steatosis and fibrosis. A random-effects model was applied to estimate pooled mean differences (MDs) and 95% confidence intervals (CIs). Results Five RCTs comprising 273 non-diabetic patients (142 in the SGLT2i group) were included. SGLT2i significantly improved liver enzymes: AST (MD = -2.03; 95% CI: -3.24 to -0.82; p < 0.01), ALT (MD = -4.50; 95% CI: -6.89 to -2.10; p < 0.01), and GGT (MD = -4.12; 95% CI: -6.87 to -1.37; p < 0.01). Modest but significant reductions were also observed in body weight (MD = -3.24 kg), BMI (MD = -1.02 kg/m²), and waist circumference (MD = -3.12 cm). However, SGLT2i did not significantly affect triglycerides, HbA1c, fasting glucose, liver stiffness, CAP scores, or FIB-4 index. Conclusion SGLT2i significantly improves liver enzyme levels and anthropometric markers in non-diabetic individuals with NAFLD/MASLD, suggesting potential therapeutic benefits. However, their effects on hepatic steatosis resolution and fibrosis progression remain inconclusive. Graphical Abstract