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

Hydrogen, as well as the halogen atom, at the 4 or 5 position in some 5‐ and 4‐nitroimidazoles were displaced by various nucleophiles such as the amino, cyano, hydroxy, and alkoxy groups. The greater reactivity of the departing group in the 4 position, which was regularly observed, is ascribed to the double activating effect of the azo and nitro groups. Cyanide ion in alcoholic solution reacted peculiarly with both 4‐ and 5‐nitroimidazoles giving o‐cyanoazoxyimidazoles as the only products. In some of the nucleophilic displacements at the 4 position of 5‐nitroimidazoles the formation of intermediate S̀‐complexes was observed.

Bei der Behandlung mit Hydroxylamin/Alkali erhält man aus den Nitro‐ imidazol‐carbonsäuren (IIa)‐(IIc) die Amino‐Verbindungen (IIIa)‐(IIIc), die durch Polyphosphorsäure (PPA) zu den Lactamen (IV) cyclisiert ′werden i können.

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