Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška Cesta 7, 1000, Ljubljana, Slovenia.
Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloška Cesta 7, 1000, Ljubljana, Slovenia.
Cardiovasc Diabetol. 2018 Dec 3;17(1):153. doi: 10.1186/s12933-018-0797-6.
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.
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.
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.
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.
动脉功能恶化和心血管事件高发是糖尿病的特征。二甲双胍和最近的降糖药物 SGLT2 抑制剂可降低心血管事件的发生。我们探讨了恩格列净在二甲双胍治疗基础上对 1 型糖尿病（T1DM）患者内皮功能和动脉僵硬度参数的可能影响。
40 例 T1DM 患者随机分为三组治疗：（1）恩格列净（25mg/d）；（2）二甲双胍（2000mg/d）；（3）恩格列净/二甲双胍（25mg/d 和 2000mg/d）。第四组接受安慰剂。治疗 12 周后，通过以下方法评估动脉功能：内皮功能[肱动脉血流介导的舒张（FMD）、反应性充血指数（RHI）]、动脉僵硬度[脉搏波速度（PWV）和颈总动脉僵硬度（β-僵硬度）]。统计分析采用单因素方差分析和 Bonferroni 事后检验。
恩格列净联合二甲双胍治疗可显著改善内皮功能，二甲双胍治疗 12 周后内皮功能也显著改善：FMD 增加 2.6 倍（P<0.001）和 RHI 增加 1.4 倍（P<0.01）。与二甲双胍相比，恩格列净联合二甲双胍治疗可显著改善动脉僵硬度参数，PWV 和 β-僵硬度分别改善 15.8%（P<0.01）和 36.6%（P<0.05）。二甲双胍单独治疗对动脉僵硬度没有影响。
与二甲双胍相比，恩格列净联合二甲双胍治疗可显著改善 T1DM 患者的动脉僵硬度。所有治疗组的内皮功能均得到相似改善。恩格列净似乎具有降低动脉僵硬度的特殊能力，这可以支持其在大型临床研究中观察到的心脏保护作用。
临床试验注册：NCT03639545。
