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

Mojca Lunder, Miodrag Janić, Miha Japelj, Andrej Juretič, Andrej Janež, Mišo Šabovič, Mojca Lunder, Miodrag Janić, Miha Japelj, Andrej Juretič, Andrej Janež, Mišo Šabovič

Abstract

Background: Deteriorated 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.

Methods: Forty 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.

Results: Empagliflozin 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.

Conclusion: Empagliflozin 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.

Keywords: Arterial stiffness; Empagliflozin; Empagliflozin/metformin; Endothelial function; Metformin; Vascular protection.

Figures

Fig. 1
Fig. 1
a Brachial artery flow-mediated dilation (FMD) values and b reactive hyperaemia index (RHI) at inclusion in the study (day 0; white columns) and after 12 weeks of treatment (grey columns) in groups treated with empagliflozin 25 mg daily (EMPA), metformin 2000 mg daily (MET) or empagliflozin/metformin (EMPA/MET). *P < 0.05; **P < 0.01; ***P < 0.001 for comparison with initial values at the beginning of the treatment in separate groups
Fig. 2
Fig. 2
a Pulse wave velocity (PWV); and b β-stiffness of common carotid artery changes (expressed in percent) in the groups treated with empagliflozin 25 mg daily (EMPA), metformin 2000 mg daily (MET) or empagliflozin/metformin (EMPA/MET). **P < 0.01; ***P < 0.001 for comparison with the metformin group

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