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

Abstract

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.

Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

“…Although not licensed for this purpose, it has therefore been suggested that people with type 2 diabetes at intermediate to high risk of fibrosis should be considered for treatment with pioglitazone and/or a GLP-1 RA with evidence of benefit (291,299). Although SGLT2i therapy has also been shown to reduce elevated levels of liver enzymes and hepatic fat content in people with NAFLD, at this time there is less evidence to support use of this class of drug as treatment for NASH (300)(301)(302). NAFLD, and in particular NASH, is also associated with an increased risk of cardiovascular complications; therefore, people with NAFLD should have their cardiovascular risk factors assessed and managed to minimize this risk (303).…”

Weight loss interventions and nonalcoholic fatty liver disease: Optimizing liver outcomes

“…Although sodium-glucose cotransporter-2 inhibitors are not indicated for treating obesity, in people with T2D these agents do produce modest weight loss. A recent review concluded that, measured by noninvasive methods, they produced positive effects on hepatic steatosis, but further studies were needed to confirm any impact on hepatic fibrosis, 86 while an umbrella review of systematic reviews found a decrease, in some studies, of liver fat and liver variables of ALT and gamma-glutamyl transferase in patients with NAFLD, as well as a reduction in biopsy-proven hepatosteatosis but no evidence of liver fibrosis improvement. 87 Metformin is not indicated for weight loss, and, despite popular belief, produces minimal weight loss.…”

Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD)

“…in Asian T2DM patients with NAFLD ( 72 ). Likewise, another systematic review also confirmed the ameliorating effects of SGLT2i on LFC and liver enzyme levels ( 73 ).…”