Empagliflozin on top of metformin treatment improves arterial function in patients with type 1 diabetes mellitus

Abstract

BackgroundDeteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We explored the possible effects of empagliflozin’s effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients.MethodsForty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively). The fourth group received placebo. Arterial function was assessed at inclusion and after 12 weeks treatment by: endothelial function [brachial artery flow-mediated dilation (FMD), reactive hyperaemia index (RHI)], arterial stiffness [pulse wave velocity (PWV) and common carotid artery stiffness (β-stiffness)]. For statistical analysis one-way analysis of variance with Bonferroni post-test was used.ResultsEmpagliflozin on top of metformin treatment significantly improved endothelial function as did metformin after 12 weeks of treatment: FMD [2.6-fold (P < 0.001) vs. 1.8-fold (P < 0.05)] and RHI [1.4-fold (P < 0.01) vs. 1.3-fold (P < 0.05)]. Empagliflozin on top of metformin treatment was superior to metformin in improving arterial stiffness parameters; it significantly improved PWV and β-stiffness compared to metformin [by 15.8% (P < 0.01) and by 36.6% (P < 0.05), respectively]. Metformin alone did not influence arterial stiffness.ConclusionEmpagliflozin on top of metformin treatment significantly improved arterial stiffness compared to metformin in T1DM patients. Endothelial function was similarly improved in all treatment groups. Empagliflozin seems to possess a specific capacity to decrease arterial stiffness, which could support its cardioprotective effects observed in large clinical studies.Trial registration Clinical trial registration: NCT03639545

Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium‐glucose co‐transporter‐2 inhibitors

“…Researchers concluded that SGLT‐2 inhibitor‐mediated reduction in blood pressure and body weight, improvement of glycemia, and suppression of oxidative stress might contribute to the observed decrease in PWV . In a more recent RCT enrolling 40 patients with T1DM, it was shown that administration of empagliflozin or empagliflozin/metformin combination for 12 weeks decreased arterial stiffness by 14.3% and 15.8% ( P < .01), respectively, compared to placebo, which did not induce any change . An interesting point is that both empagliflozin and empagliflozin/metformin combination had the same effect on endothelial function, as assessed by flow‐mediated dilation (FMD) and reactive hyperemia index (RHI), leading to the conclusion that the observed improvement in arterial stiffness with empagliflozin might be independent of its effect on endothelial dysfunction …”

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