SGLT2 Inhibitors for Steatosis and Noninvasive Liver Markers in MASLD: A Meta-analysis of Randomized Trials

Abstract

Abstract Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to cardiometabolic dysfunction, yet liver-specific pharmacological options remain limited. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been proposed as potential therapeutic candidates because of their metabolic benefits, but their effects on hepatic outcomes remain uncertain. Aims: This study aimed to evaluate the effects of SGLT2 inhibitors on hepatic steatosis, non-invasive fibrosis-related markers, and liver enzymes in adults with MASLD. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials comparing SGLT2 inhibitors with placebo, standard care, or pioglitazone. Primary outcomes included MRI-PDFF, CAP, LSM, and FIB-4 index. Secondary outcomes were ALT and AST. Results: In trials with placebo or standard-of-care comparators, SGLT2 inhibitors significantly reduced CAP (MD = −21.01 dB/m, 95% CI: −41.84 to −0.18), whereas MRI-PDFF showed a non-significant reduction (MD = −7.03%, 95% CI: −18.22 to 4.16) with substantial heterogeneity. Neither LSM (MD = −0.95 kPa, 95% CI: −2.20 to 0.29) nor FIB-4 index (MD = −0.22, 95% CI: −1.54 to 1.09) improved significantly. Effects on liver enzymes were generally small and inconsistent. Compared with pioglitazone, SGLT2 inhibitors had broadly comparable effects on most hepatic outcomes, with a small reduction in FIB-4 that should be considered exploratory. Conclusions: SGLT2 inhibitors were associated with modest improvements in steatosis-related markers, particularly CAP, among predominantly diabetic MASLD populations. Evidence for improvement in MRI-PDFF and fibrosis-related outcomes remains insufficient. Their use in MASLD should be guided primarily by metabolic, cardiovascular, and renal indications rather than liver-specific therapeutic claims.