Empagliflozin promises to bridge the gap between non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease

Non-alcoholic fatty liver disease (NAFLD) represents the commonest chronic liver disease in the Western world, while its prevalence among patients with type 2 diabetes (T2D) is as much as 70% [1]. Non-alcoholic fatty liver disease shares common pathophysiologic mechanisms with T2D, mainly insulin resistance, lipotoxicity, and inflammation [2].
Besides the well-established role of T2D in the development of cardiovascular disease (CVD) [3], NAFLD has also emerged as a potential predictor of CVD. Previous data support the association between NAFLD and subclinical atherosclerosis, with a remarkable higher probability of its presence among patients with NAFLD compared to controls (OR = 1.60, 95% CI: 1.45–1.78) [4]. Increased arterial stiffness [5], coronary artery calcification [6], elevated carotid intimal media thickness [7], and impaired endothelial function [8] have been previously shown in patients with NAFLD.
Targher et al. have demonstrated that patients with NAFLD exhibit almost 64% greater probability of experiencing fatal or non-fatal CVD events, compared to controls (OR = 1.64, 95% CI: 1.26–2.13) [9]. Similar results were obtained from another meta-analysis conducted by Mahfood Haddad et al., who demonstrated a significantly higher risk of clinical cardiovascular events in patients with NAFLD compared to controls – up to 77% (RR = 1.77, 95% CI: 1.26–2.48) [10]. According to a recently published retrospective, cohort study involving 1452 patients with NAFLD and T2D, the risk of CVD among those patients was almost 70% higher compared to patients with no liver disease (HR = 1.70, 95% CI: 1.52–1.90) and was associated with a 60% greater risk of all-cause mortality [11].
However, it is worth mentioning that the observational design of the included studies in the aforementioned meta-analyses does not permit safe conclusions to be drawn regarding the true causal relationship between NAFLD and CVD. It is still debated whether NAFLD represents a true predictor of CVD, while causality has to be proven in large-scale, prospective clinical studies [12].
Recent data suggest that liver fat content represents a risk factor for CVD [13]; however, proceeding a step further, the fibrosis stage seems to be the strongest predictor of both overall and disease-specific (including cardiovascular) mortality in patients with NAFLD/non-alcoholic steatohepatitis (NASH). Patients with liver fibrosis stage 3–4, irrespective of NAFLD activity score,...


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