Halimi Jean-Michel
Service de néphrologie-HTA, dialyses et transplantation rénale, hôpital Bretonneau, CHU de Tours, 2, boulevard Tonnellé, 37044 Tours cedex, France.
Nephrol Ther. 2021 Jun;17(3):143-148. doi: 10.1016/j.nephro.2020.12.006. Epub 2021 Mar 25.
Since 2015, 10 randomized clinical trials assessed the cardiovascular safety of SGLT2 inhibitors, and then assessed the potential renal and cardiovascular benefits of these drugs (EMPAREG Outcome, CANVAS, DECLARE, DAPA-HF, CREDENCE, EMPEROR-reduced, VERTIS, DAPA-CKD, SCORED, SOLOIST-WHF) in over 88,000 patients. The results of EMPAREG Outcome showed major renal and cardiovascular protection but they were unexpected. The other trials regarding the effects of dapagliflozin, canagliflozin, empagliflozin and more recently sotagliflozin have confirmed most of these results and extended them to other populations. There is no scientific doubt that these drugs confer a marked renal protection in patients already treated with renin angiotensin system blockers (reduction of the risk of end-stage renal disease: -35 to 40%) et reduce the risk of hospitalization for heart failure (-30 to 35%), especially in patients with heart failure with reduced ejection fraction. The benefit/risk profile is highly favorable but minor (genital candidosis, urinary tract infections, euglycemic acido-ketosis) and serious (Fournier gangrene) side effects must not be forgotten. Renal protection is twice the effect of renin angiotensin system blockers, and is maintained in patients already treated with them, in patients with GFR 25mL/min/1.73m and over, regardless of whether they have type 2 diabetes mellitus or not (of note, patients with type 1 diabetes mellitus, polycystic kidney disease, lupus and vasculitis were excluded in these studies). Reduction of the incidence of heart failure is similar to that observed with sacubitril/valsartan, and is maintained in patients already treated with sacubitril/valsartan. SGLT2 inhibitors have now defined a new standard of care, and it will be necessary to explore the proper use of the new mineralocorticoid receptor antagonist finerenone that demonstrated significant renal and cardiovascular protection in mostly SGLT2 inhibitors-untreated diabetic patients with chronic kidney disease (or even some GLP-1 agonists). A new era for our patients.
自2015年以来，10项随机临床试验评估了SGLT2抑制剂的心血管安全性，随后在超过88000名患者中评估了这些药物（EMPAREG Outcome、CANVAS、DECLARE、DAPA-HF、CREDENCE、EMPEROR-reduced、VERTIS、DAPA-CKD、SCORED、SOLOIST-WHF）潜在的肾脏和心血管益处。EMPAREG Outcome的结果显示出主要的肾脏和心血管保护作用，但这些结果出人意料。其他关于达格列净、卡格列净、恩格列净以及最近索格列净作用的试验证实了其中大部分结果，并将其扩展到其他人群。毫无疑问，这些药物在已经接受肾素血管紧张素系统阻滞剂治疗的患者中具有显著的肾脏保护作用（降低终末期肾病风险：-35%至40%），并降低心力衰竭住院风险（-30%至35%），尤其是在射血分数降低的心力衰竭患者中。其获益/风险比非常有利，但轻微（生殖器念珠菌病、尿路感染、正常血糖性酮症酸中毒）和严重（福尼尔坏疽）的副作用也不容忽视。肾脏保护作用是肾素血管紧张素系统阻滞剂的两倍，并且在已经接受其治疗的患者、肾小球滤过率（GFR）为25mL/min/1.73m及以上的患者中持续存在，无论他们是否患有2型糖尿病（值得注意的是，这些研究排除了1型糖尿病、多囊肾病、狼疮和血管炎患者）。心力衰竭发生率的降低与沙库巴曲/缬沙坦观察到的相似，并且在已经接受沙库巴曲/缬沙坦治疗的患者中持续存在。SGLT2抑制剂现已定义了一种新的治疗标准，有必要探索新型盐皮质激素受体拮抗剂非奈利酮的合理使用，该药物在大多数未接受SGLT2抑制剂治疗的慢性肾病糖尿病患者（甚至一些胰高血糖素样肽-1激动剂）中显示出显著的肾脏和心血管保护作用。这是我们患者的一个新时代。
