NON-ALCOHOLIC fatty liver disease (NAFLD) is a prevalent chronic liver condition, characterised by excessive fat accumulation in the liver without significant alcohol consumption. NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma. It is closely linked to metabolic disorders such as obesity, insulin resistance, and type 2 diabetes mellitus (T2DM), affecting over 50% of diabetic individuals.
The connection between T2DM and NAFLD is primarily driven by insulin resistance, which increases free fatty acid levels and contributes to hepatic fat accumulation. Elevated blood glucose and dyslipidaemia exacerbate liver damage, underscoring the need for treatments targeting both conditions.
Empagliflozin, an SGLT2 inhibitor used in T2DM management, reduces glucose reabsorption in the kidneys, increasing urinary glucose excretion and lowering blood glucose levels. Beyond glycaemic control, empagliflozin has shown benefits such as weight loss, reduced blood pressure, and improved cardiovascular outcomes. Emerging evidence suggests its potential role in improving liver health in NAFLD and NASH, although the mechanisms remain under study.
Preclinical studies indicate that empagliflozin reduces liver fat, improves liver function markers, and decreases inflammation. Clinical trials report reductions in liver enzymes (ALT, AST) and markers of fibrosis in NAFLD patients, potentially through improved insulin sensitivity, lipid metabolism, and reduced systemic inflammation.
Despite promising data, empagliflozin’s impact on NAFLD in T2DM remains inconclusive. Some studies report significant liver function improvements, while others show mixed results due to variations in study design and patient populations. A recent study showed a significant reduction in liver fat grade in empagliflozin-treated patients, though a meta-analysis by Tang et al. (2022) found no significant improvements in hepatic steatosis or lipid metabolism markers.
A recent consensus suggests replacing NAFLD with metabolic dysfunction-associated steatotic liver disease (MASLD) when at least one cardiometabolic risk factor is present. Given that all study participants had T2DM, this study classified the condition as MASLD. While empagliflozin demonstrated benefits, further research is needed to confirm its role in NAFLD/MASLD management.
Empagliflozin also reduced systolic blood pressure, reinforcing its cardiovascular benefits. Given the high prevalence of hypertension in T2DM and NAFLD, this adds to its therapeutic potential.
In conclusion, while empagliflozin shows promise in improving liver health in T2DM patients with NAFLD/MASLD, further large-scale studies are needed to confirm its efficacy and clinical significance.
Katie Wright, EMJ
Reference
Shojaei F et al. The effect of empagliflozin on non-alcoholic fatty liver disease-related parameters in patients with type 2 diabetes mellitus: a randomized controlled trial. BMC Endocr Disord. 2025;25(1):52.
