EFFECT OF SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS ON ARTERIAL STIFFNESS UNDER STATIC OR AMBULATORY CONDITIONS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract

Objective: Arterial stiffness represents an emerging cardiovascular risk factor with independent prognostic implications. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a novel drug class with significant cardio-protective effects, but largely unknown mechanism underlying this effect. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV), the “gold-standard’’ measure of arterial stiffness. 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 or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus placebo or active comparator and addressing their effect on PWV under static or ambulatory conditions. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. Results: We pooled data from 4 trials for a total of 301 enrolled participants assigned either to SGLT-2 inhibitor or control. Treatment with a SGLT-2 inhibitor compared to placebo or active control led to a significant decrease in PWV by 0.25 m/s (mean difference = -0.25, 95% CI; -0.49 to -0.01, I2 = 24%, p = 0.04). Certainty of evidence was graded as low. Conclusions: SGLT-2 inhibitors produce a slight, however statistically significant decrease in PWV in patients with established cardiovascular disease or cardiovascular risk factors, such as hypertension and T2DM.