SGLT2 inhibitors for non-diabetic kidney disease : drugs to treat CKD that also improve glycaemia
Fernández-Fernández, Beatriz (Universidad Autónoma de Madrid)
Sarafidis, Pantelis (Aristotle University of Thessaloniki)
Kanbay, Mehmet (Hospital Universitari de Bellvitge)
Navarro-González, Juan F. (Hospital Universitario Nuestra Señora de Candelaria (Santa Cruz de Tenerife))
Soler, María José (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Górriz, Jose Luis (Hospital Clínic Universitari (València))
Ortiz, Alberto (Universidad Autónoma de Madrid)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	Sodium-glucose co-transporter-2 (SGLT2) inhibitors decreased cardiovascular (CV) events and improved renal outcomes in CV safety studies in type 2 diabetes melitus (T2DM) patients at high CV risk. Canagliflozin also improved kidney outcomes in diabetic kidney disease in the Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluationtrial. More recently, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial showed that dapagliflozin improved CV outcomes in patients with HF with or without diabetes. Protection from HF in non-diabetics was confirmed for empagliflozin in the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. A meta-analysis of DAPA-HF and EMPEROR-Reduced confirmed reductions in all-cause and CV death and the combined risk of CV death or worsening HF, as well as in the composite renal endpoint {hazard ratio [HR] 0. 62 [95% confidence interval (CI) 0. 43-0. 90]} without differences based on the presence of diabetes or baseline estimated glomerular filtration rate (eGFR). Moreover, the Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (DAPA-CKD) showed that dapagliflozin as an add-on over renin-angiotensin system blockade in patients with chronic kidney disease (CKD; with or without T2DM) reduced the HR for the primary endpoint (time to the first occurrence of ≥50% eGFR decline, end-stage kidney disease or renal or CV death) to 0. 61 (95% CI 0. 51-0. 72) and for the secondary endpoints of worsening renal function or death from kidney failure [HR 0. 56 (95% CI 0. 45-0. 68)], hospitalization for HF or CV death [HR 0. 71 (95% CI 0. 55-0. 92)] and all-cause mortality [HR 0. 69 (95% CI 0. 53-0. 88)]. These beneficial effects were consistent in patients with and without T2DM. In conclusion, SGLT2 inhibitors offer CV and kidney protection in both diabetic and non-diabetic CKD and, additionally, improve glycaemic control in T2DM, making them first-line therapy for CKD independent from diabetic status.
Grants:	Instituto de Salud Carlos III PI17/00257 Instituto de Salud Carlos III PI18/01386 Instituto de Salud Carlos III PI19/00588 Instituto de Salud Carlos III PI19/00815 Instituto de Salud Carlos III DTS18/00032 Instituto de Salud Carlos III AC18/00064 Instituto de Salud Carlos III AC18/00071 Instituto de Salud Carlos III RD016/0009
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article de revisió ; recerca ; Versió publicada
Subject:	Chronic kidney disease ; Clinical trials ; Mortality ; Outcomes ; SGLT2 inhibitor
Published in:	Clinical Kidney Journal, Vol. 13 Núm. 5 (october 2020) , p. 728-733, ISSN 2048-8513

DOI: 10.1093/ckj/sfaa198
PMID: 33123352

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