Meta-Analysis Addressing the Effect of Sodium-Glucose Co-Transporter-2 Inhibitors on Flow-Mediated Dilation in Patients With Type 2 Diabetes Mellitus

Abstract

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.