SGLT2 inhibitors for improving hepatic fibrosis and steatosis in non-alcoholic fatty liver disease complicated with type 2 diabetes mellitus: a systematic review

Aim of the study
To evaluate the efficacy of sodium/glucose cotransporter-2 inhibitors (SGLT2i) in improving hepatic fibrosis and steatosis of non-alcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM).

Material and methods
We searched CENTRAL, MEDLINE, and EMBASE and included any clinical trials involving patients with NAFLD and T2DM aged ≥ 18 years comparing efficacy of SGLT2i and other antidiabetic drugs in improving fibrosis and steatosis, irrespective of publication status, year of publication, and language.

Results
Five clinical trials were included. One study reported significant improvements in the controlled attenuation parameter 314.6 ±61.0 dB/m to 290.3 ±72.7 dB/m (p = 0.04) in the SGLT2i group measured by transient elastography. In patients with significant fibrosis, dapagliflozin treatment significantly decreased the liver stiffness measurement from 14.7 ±5.7 kPa at baseline to 11.0 ±7.3 kPa after 24 weeks (p = 0.02). One study reported a significant decrease in liver fat content 16.2% to 11.3% (p < 0.001) in the SGLT2i group compared to the control (p < 0.001). Three studies reported significant improvement in the liver-to-spleen ratio in the SGLT2i group after treatment 0.96 (0.86-1.07) to 1.07 (0.98-1.14), p < 0.01, 0.80 ±0.24 to 1.00 ±0.18, p < 0.001, and 0.91 (0.64-1.04) to 1.03 (0.80-1.20), p < 0.001 respectively. All studies reported a significant decrease in alanine aminotransferase with SGLT2i.

Conclusions
SGLT2i is associated with positive effects on hepatic steatosis measured by non-invasive modalities. Further studies are needed to confirm the impact of SGLT2i on hepatic fibrosis and steatosis.