Effect of SGLT-2 inhibitors on liver fibrosis progression in patients with MASLD: an updated meta-analysis based on RCTs.

Abstract

<h4>Background</h4>The purpose of our study was to assess the effect of sodium-glucose cotransporter protein 2 (SGLT-2) inhibitors on the progression of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), which is currently renamed metabolic dysfunction-associated steatohepatitis (MASLD).<h4>Methods</h4>From database establishment to February 2025, we systematically searched electronic databases, including PubMed, Web of Science, Embase, and the Cochrane Library, to identify relevant randomized controlled trials (RCTs). The mean difference (MD) and 95% confidence intervals (CIs) were used to assess the effects of SGLT-2 inhibitors on liver fibrosis indicators, including the Fib-4 index, NAFLD fibrosis score (NFS), liver stiffness measurement (LSM), controlled attenuation parameter (CAP), and serum type 4 collagen 7s levels.<h4>Results</h4>A total of 16 RCTs involving 11,300 subjects were included. The meta-analysis revealed that, compared with the control group, SGLT-2 inhibitors significantly reduced the Fib-4 index (MD = -0.16, 95% CI: -0.32 to 0.00, <i>p</i> = 0.05), NFS (MD = -0.10, 95% CI: -0.16 to -0.04, <i>p</i> = 0.01) and serum type 4 collagen 7s levels (MD = -0.35, 95% CI: -0.63 to -0.06, <i>p</i> = 0.02) in NAFLD patients. However, no significant differences were observed in imaging metrics such as LSM and CAP. Subgroup analyses indicated that empagliflozin and ipragliflozin may be more efficacious, with their benefits more pronounced in patients receiving short-term treatment (<24 weeks) and those with combined T2DM.<h4>Conclusion</h4>SGLT-2 inhibitors may delay the progression of liver fibrosis in patients with MASLD, particularly by improving serologic parameters. However, additional high-quality studies are needed to validate their clinical value.