The Effects of Sodium-Glucose Cotransporter 2-Inhibitors on Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease or Steatohepatitis and Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials

Abstract

Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are part of metabolic syndrome and share multiple causal associations. Both conditions have an alarmingly increasing incidence and lead to multiple complications, which have an impact on a variety of organs and systems, such as the kidneys, eyes, and nervous and cardiovascular systems, or may cause metabolic disruptions. Sodium-glucose cotransporter 2-inhibitors (SGLT2-i), as an antidiabetic class with well-established cardiovascular benefits, and its class members have also been studied for their presumed effects on steatosis and fibrosis improvement in patients with NAFLD or non-alcoholic steatohepatitis (NASH). The MEDLINE and Cochrane databases were searched for randomized controlled trials examining the efficacy of SGLT2-i on the treatment of NAFLD/NASH in patients with T2DM. Of the originally identified 179 articles, 21 articles were included for final data analysis. Dapagliflozin, empagliflozin, and canagliflozin are some of the most used and studied SGLT2-i agents which have proven efficacy in treating patients with NAFLD/NASH by addressing/targeting different pathophysiological targets/mechanisms: insulin sensitivity improvement, weight loss, especially visceral fat loss, glucotoxicity, and lipotoxicity improvement or even improvement of chronic inflammation. Despite the considerable variability in study duration, sample size, and diagnostic method, the SGLT2-i agents used resulted in improvements in non-invasive markers of steatosis or even fibrosis in patients with T2DM. This systematic review offers encouraging results that place the SGLT2-i class at the top of the therapeutic arsenal for patients diagnosed with T2DM and NAFLD/NASH.

Time for micro-RNAs in steatotic liver disease: a case–control study

“…MiR-192 could be the link between liver fibrosis and diabetic nephropathy (DN) as it is upregulated not only in our MAFLD patients but also in DN patients ( 35 ). The presence of T2DM could be one of the predictors of rapid fibrotic progression ( 36 ), and miR-192 might be one of the important biomarkers for disease evolution in MAFLD and DN.…”

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis

“…Ursodeoxycholic acid (UDCA) is a naturally occurring bile acid that is traditionally used to treat primary biliary cholangitis. 94 Due to its cytoprotective, immunomodulatory, and anti-apoptotic properties, there is growing interest in exploring its use in treating other liver diseases, such NAFLD. 95 , 96 Preliminary studies have posited that UDCA may improve liver function and reduce liver cell damage in NAFLD by stabilizing cell membranes, reducing harmful bile acids, and protecting against oxidative stress.…”

“…[91][92][93] Specific research on tofogliflozin has shown its ability to reduce liver fat and improve indicators of liver damage in patients with both NAFLD and T2DM. 94 One trial compared tofogliflozin with glimepiride, focusing on their effects on liver histology and metabolic markers in NAFLD patients with T2DM over a 48-week period.…”

Progress in the Study of the Hepatoprotective Effect of SGLT2i on NAFLD Patients with T2DM

“…A meta-analysis showed that the use of SGLT2-i improved non-invasive markers of steatosis and even fibrosis in T2DM patients. It is also believed that SGLT2-i drugs may be the first choice for patients diagnosed with T2DM and NAFLD/NASH [40].…”