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

**Authors:** Lei Yang, Jiale Ruan, Yingying Fang, Anyi Xu

PMC · DOI: 10.3389/fmed.2025.1667823 · Frontiers in Medicine · 2026-01-20

## TL;DR

This study finds that SGLT-2 inhibitors may slow liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis.

## Contribution

An updated meta-analysis of RCTs reveals SGLT-2 inhibitors' potential to reduce liver fibrosis markers in MASLD patients.

## Key findings

- SGLT-2 inhibitors significantly reduced Fib-4 index, NFS, and serum type 4 collagen 7s levels in MASLD patients.
- No significant changes were observed in liver stiffness or controlled attenuation parameters.
- Empagliflozin and ipragliflozin showed greater efficacy in short-term treatment and in patients with T2DM.

## Abstract

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).

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.

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, p = 0.05), NFS (MD = −0.10, 95% CI: −0.16 to −0.04, p = 0.01) and serum type 4 collagen 7s levels (MD = −0.35, 95% CI: −0.63 to −0.06, p = 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.

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.

## Linked entities

- **Proteins:** SLC5A2 (solute carrier family 5 member 2), FIB4 (Plastid-lipid associated protein PAP / fibrillin family protein), NFS (cysteine desulfurase, putative), LSM (like-sm protein), CTAA1 (cataract, anterior polar 1)
- **Chemicals:** empagliflozin (PubChem CID 11949646), ipragliflozin (PubChem CID 10453870)
- **Diseases:** non-alcoholic fatty liver disease (MONDO:0013209), metabolic dysfunction-associated steatohepatitis (MONDO:0007027), T2DM (MONDO:0005148)

## Full-text entities

- **Genes:** SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}
- **Diseases:** metabolic dysfunction-associated steatohepatitis (MESH:D005234), NAFLD (MESH:D065626), fibrosis (MESH:D005355), liver fibrosis (MESH:D008103)
- **Chemicals:** ipragliflozin (MESH:C572941), empagliflozin (MESH:C570240)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12864471/full.md

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Source: https://tomesphere.com/paper/PMC12864471