LAUSR

OBJECTIVE Endothelial dysfunction seems to play a pivotal role in the pathogenesis of cardiovascular disease and related complications among high-risk patients, such as those suffering from type 2 diabetes mellitus (T2DM). Non-invasive peripheral endothelial function assessment with measurement of brachial artery flow-mediated dilation (FMD) has been demonstrated to predict adverse cardiovascular events. Herein, we sought to determine whether SGLT-2 inhibitors provide a significant effect on endothelial function, as assessed through FMD. DESIGN AND METHOD We searched PubMed, Cochrane Library and grey literature from inception to 10th October 2021 for parallel group randomized controlled trials (RCTs) enrolling adult subjects with T2DM, assigned to a SGLT-2 inhibitor versus placebo or active comparator and addressing their effect on FMD. We set as primary efficacy outcome the change in FMD with SGLT-2 inhibitor versus control. RESULTS We pooled data from 4 trials in a total of 270 subjects with T2DM. We demonstrated that treatment with SGLT-2 inhibitor versus placebo or active comparator produced a significant increase in FMD by 1.66% (95% CI; 0.56 - 2.76, I2 = 28%, p = 0.003). Notably, all eligible RCTs utilized dapagliflozin. Overall risk of bias was evaluated as low across the selected studies. CONCLUSIONS The present meta-analysis demonstrated a clear benefit on endothelial function with SGLT-2 inhibitors compared to placebo or active comparator. Although the sample size is small, it seems that amelioration of endothelial dysfunction with SGLT-2 inhibitors constitutes another significant mechanism that confers to cardio-protection with this drug class. Larger RCTs will shed further light on this important pathophysiologic link.