Les inhibiteurs du SGLT2 : une nouvelle ère pour nos patients

Abstract

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/1.73m2 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.