# Efficacy of empagliflozin in patients with metabolic dysfunction-associated steatotic liver disease with or without diabetes: a systematic review and meta-analysis of randomized controlled trials

**Authors:** Khalid I. AlHussaini

PMC · DOI: 10.3389/fmed.2025.1712586 · Frontiers in Medicine · 2026-02-04

## TL;DR

Empagliflozin, a diabetes drug, lowers liver enzymes and triglycerides in people with fatty liver disease, but does not improve liver scarring or fat levels.

## Contribution

This study is the first meta-analysis to systematically evaluate empagliflozin's effects on both hepatic and metabolic outcomes in MASLD patients with or without diabetes.

## Key findings

- Empagliflozin significantly reduced ALT and AST levels in MASLD patients.
- Triglyceride levels were significantly reduced with empagliflozin treatment.
- No significant changes were observed in non-invasive markers of liver fibrosis or steatosis.

## Abstract

Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has demonstrated potential hepatic benefits in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), particularly among those with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to evaluate the efficacy of empagliflozin on hepatic and metabolic outcomes in patients with MASLD.

A systematic literature search of PubMed, Scopus, and Web of Science was conducted up to September 2025 to identify randomized controlled trials (RCTs) evaluating empagliflozin in MASLD patients with or without T2DM. Primary outcomes included changes in liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic steatosis and fibrosis indices including controlled attenuation parameter (CAP), liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), and the MASLD fibrosis score (NFS), and secondary outcomes included lipid parameters, glycemic control, and anthropometric measures.

Eight RCTs involving 672 participants (353 empagliflozin and 319 placebo) were included. Empagliflozin significantly reduced ALT (mean difference [MD] = −9.36, 95% CI: −16.07 to −2.66, p = 0.006) and AST (MD = −9.09, 95% CI: −15.41 to −2.78, p = 0.005) compared to placebo. A significant reduction was also observed in triglyceride levels (MD = −29.29, 95% CI: −53.14 to −5.45, p = 0.02). No significant differences were found for CAP (MD = −5.72, p = 0.29), LSM (MD = −0.49, p = 0.38), APRI (MD = −0.02, p = 0.36), FIB-4 (MD = −0.06, p = 0.34), or NFS (MD = −0.04, p = 0.83). Similarly, no significant effects were observed for body weight, body mass index (BMI), fasting blood sugar, or glycated hemoglobin (HbA1c).

Empagliflozin is associated with significant improvements in liver enzyme levels and a reduction in triglyceride levels in patients with MASLD. However, no clear benefit was observed in non-invasive markers of hepatic steatosis or fibrosis. Further large-scale, long-duration RCTs with histological endpoints are needed to confirm these findings and establish empagliflozin’s role in MASLD management.

## Linked entities

- **Chemicals:** empagliflozin (PubChem CID 11949646)
- **Diseases:** metabolic dysfunction-associated steatotic liver disease (MONDO:0013209), type 2 diabetes mellitus (MONDO:0005148)

## Full-text entities

- **Genes:** THRB (thyroid hormone receptor beta) [NCBI Gene 7068] {aka C-ERBA-2, C-ERBA-BETA, ERBA2, GRTH, NR1A2, PRTH}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}
- **Diseases:** weight loss (MESH:D015431), yeast infections (MESH:D002181), insulin resistance (MESH:D007333), HCC (MESH:D006528), CAP (MESH:C538265), T2D (MESH:D003924), adiposity (MESH:D018205), hepatic injury (MESH:D056486), LSM (MESH:D017093), NAFLD (MESH:D065626), diabetes (MESH:D003920), hepatic fibrosis (MESH:D008103), adipose tissue inflammation (MESH:D007249), sarcopenia (MESH:D055948), MASLD (MESH:D008107), cirrhosis (MESH:D005355), dyslipidemia (MESH:D050171), glucosuria (MESH:D006030), Metabolic dysfunction-associated (MESH:D008659), fat (MESH:D004620), visceral adiposity (MESH:D007418), MASH (MESH:D005234), obesity (MESH:D009765), non-alcoholic steatohepatitis (MESH:D005235)
- **Chemicals:** dapagliflozin (MESH:C529054), GLP-1 receptor agonists (-), glucose (MESH:D005947), resmetirom (MESH:C588408), lipid (MESH:D008055), ipragliflozin (MESH:C572941), pioglitazone (MESH:D000077205), uric acid (MESH:D014527), triglyceride (MESH:D014280), blood glucose (MESH:D001786), Empagliflozin (MESH:C570240), luseogliflozin (MESH:C549343)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

16 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12914734/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12914734/full.md

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Source: https://tomesphere.com/paper/PMC12914734