Effect of sodium-glucose co-transporter-2 inhibitors on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials.

Abstract

Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.