Abstract
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disorder worldwide. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucose-lowering agents with cardiovascular benefits, have shown hepatoprotective potential. Their comparative effects on steatosis and fibrosis, their interrelationship, and the role of treatment duration remain uncertain. OBJECTIVES: To compare the effects of individual SGLT2 inhibitors on hepatic steatosis and fibrosis, and to assess correlations between controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as well as the impact of treatment duration. METHODS: Randomized controlled trials of SGLT2 inhibitors in MASLD were synthesized using Bayesian network meta-analysis. Hepatic steatosis (CAP) and fibrosis (LSM) were analyzed separately as mean differences (MDs) with 95% credible intervals (CrIs). Prespecified study-level effect modifiers were evaluated using Bayesian network meta-regression. Comparative rankings were derived using the surface under the cumulative ranking curve (SUCRA). Trial-level concordance between CAP and LSM was assessed using bivariate Bayesian meta-analysis. RESULTS: Fourteen RCTs (n = 855) were included. Compared with standard care, SGLT2 inhibitors reduced CAP (MD 10.48 dB/m; 95% CrI 0.53 to 18.72) and LSM (MD 0.57 kPa; 95% CrI 0.02 to 1.12). Dapagliflozin showed the most consistently favorable estimates across both outcomes. Trial-level treatment effects on CAP and LSM were highly concordant. Treatment duration was not significantly associated with treatment effects; most trials lasted ≤ 24 weeks. CONCLUSIONS: SGLT2 inhibitors, particularly dapagliflozin, were associated with improvements in non-invasive markers of steatosis and fibrosis in MASLD. CAP and LSM show aligned trends but remain biologically distinct, underscoring the need for longer, histology-driven, multiethnic trials to confirm true antifibrotic efficacy. REGISTRATION: PROSPERO CRD420251146413.