Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure

查看全文 作　　者：Petra Grubić [1]Rotkvić;Maja Cigrovski [2,3]Berković;Nikola [4]Bulj;Luka [5]Rotkvić;Ivana [6]Ćelap

机构地区：[1]Department of Cardiology,University Hospital,10000 Zagreb,Croatia;[2]Department of Endocrinology,Diabetes,Metabolism and Clinical Pharmacology,University Hospital,Zagreb 10000,Croatia;[3]Department for Medicine of Sports and Exercise,Faculty of Kinesiology University of Zagreb,Zagreb 10000,Croatia;[4]Department of Cardiology,University Hospital Centre,Zagreb 10000,Croatia;[5]Department of Cardiology,Magdalena Clinic for Cardiovascular Disease,Krapinske Toplice 49217,Croatia;[6]Department of Clinical Chemistry,University Hospital Centre,Zagreb 10000,Croatia

出　　处：《World Journal of Diabetes》索引2020年第11卷第7期,共11页

摘　　要：Three major cardiovascular outcome trials(CVOTs)with a new class of antidiabetic drugs-sodium-glucose cotransporter 2(SGLT2)inhibitors(EMPAREG OUTCOME trial with empagliflozin,CANVAS Program with canagliflozin,DECLARE-TIMI 58 with dapagliflozin)unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk,which seems to be the most sensitive outcome of SGLT2 inhibition.No other CVOT to date has shown any significant benefit on heart failure events.Even more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure:Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes status.Nevertheless,despite their possible wide clinical implications,there is much doubt about the mechanisms of action and a lot of questions to unravel,especially now when their benefits translated to nondiabetic patients,rising doubts about the validity of some current mechanistic assumptions.The time frame of their cardiovascular benefits excludes glucoselowering and antiatherosclerotic-mediated effects and multiple other mechanisms,direct cardiac as well as systemic,are suggested to explain their early cardiorenal benefits.These are:Anti-inflammatory,antifibrotic,antioxidative,antiapoptotic properties,then renoprotective and hemodynamic effects,attenuation of glucotoxicity,reduction of uric acid levels and epicardial adipose tissue,modification of neurohumoral system and cardiac fuel energetics,sodiumhydrogen exchange inhibition.The most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure pathogenesis.All the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text. 关键词：Sodium-glucose cotransporter 2 inhibitors Heart failure Cardiovascular outcomes Diabetes mellitus Physiological mechanisms Pleiotropic effects

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Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure

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