# Empagliflozin and its impact on hepatic and metabolic outcomes in patients with type 2 diabetes and NAFLD: a systematic review and meta-analysis

**Authors:** Khadeeja Ali Hamzah, Mohammedsadeq A. Shweliya, Yousif Hameed Kurmasha, Marafi Jammaa Ahmed, Ashna Habib, Abanoub I.I. Kamel, Zarwa Rashid, Aya Ahmed Shimal, Mayar Moghazy, Fatima Fahem, Mohammad Yassin Al Aboud, Ahmed Elgazzar, Abdulhadi M. A. Mahgoub, Ali Saad Al-Shammari

PMC · DOI: 10.1186/s13098-025-02084-x · Diabetology & Metabolic Syndrome · 2026-01-08

## TL;DR

Empagliflozin, a diabetes drug, reduces liver fat and improves metabolic markers in patients with type 2 diabetes and fatty liver disease, but its impact on liver fibrosis is unclear.

## Contribution

This is the first systematic review and meta-analysis evaluating empagliflozin's effects on both hepatic and metabolic outcomes in T2DM with MASLD.

## Key findings

- Empagliflozin significantly reduced liver fat and stiffness in patients with T2DM and MASLD.
- The drug improved glycemic control, weight, and uric acid levels but did not significantly affect fibrosis or inflammation markers.
- Larger, long-term trials are needed to confirm the drug's effects on liver fibrosis.

## Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease (NAFLD), often coexists with type 2 diabetes mellitus (T2DM) due to shared metabolic pathways such as insulin resistance. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, may provide hepatic and metabolic benefits. This study evaluated its effects on liver fat, enzymes, fibrosis, metabolic parameters, and inflammation in T2DM with MASLD.

A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed according to PRISMA guidelines. Primary outcomes included liver fat content, enzymes, and fibrosis markers. Secondary outcomes were metabolic and inflammatory parameters.

Eleven RCTs (n = 3077) were included. Empagliflozin significantly reduced liver fat (MD = -3.11%; 95% CI: -4.12 to -2.11; p < 0.00001) and liver stiffness (MD = -0.43 kPa; p = 0.003), but had no significant effect on AST (-0.27 IU/L; p = 0.89) or GGT (-9.25 IU/L; p = 0.14). It significantly lowered HbA1c (-0.54%; p < 0.0001), fasting glucose (-20.89 mg/dL; p < 0.0001), weight (-2.04 kg; p < 0.0001), and waist circumference (-3.47 cm; p < 0.0001), with a nonsignificant reduction in BMI (-0.77 kg/m²; p = 0.09).Uric acid decreased (-0.41 mg/dL; p < 0.00001), but IL-6 and fibrosis scores (FIB-4, NFS) remained unchanged.

Empagliflozin improves liver fat, stiffness, glycemic control, body weight, and uric acid in T2DM with MASLD, but its effects on fibrosis and inflammation remain uncertain. Larger, long-term histologic trials are needed to confirm these outcomes.

## Linked entities

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

## Full-text entities

- **Genes:** SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}
- **Diseases:** MASLD (MESH:D008107), NAFLD (MESH:D065626), T2DM (MESH:D003924), insulin resistance (MESH:D007333), fibrosis (MESH:D005355), inflammation (MESH:D007249)
- **Chemicals:** Uric acid (MESH:D014527), glucose (MESH:D005947), Empagliflozin (MESH:C570240)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

21 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12879374/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12879374/full.md

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Source: https://tomesphere.com/paper/PMC12879374