TY - JOUR

T1 - SGLT2 Inhibition for CKD and Cardiovascular Disease in Type 2 Diabetes

T2 - Report of a Scientific Workshop Sponsored by the National Kidney Foundation

AU - Tuttle, Katherine R

AU - Brosius, Frank C

AU - Cavender, Matthew A

AU - Fioretto, Paola

AU - Fowler, Kevin J

AU - Heerspink, Hiddo J L

AU - Manley, Tom

AU - McGuire, Darren K

AU - Molitch, Mark E

AU - Mottl, Amy K

AU - Perreault, Leigh

AU - Rosas, Sylvia E

AU - Rossing, Peter

AU - Sola, Laura

AU - Vallon, Volker

AU - Wanner, Christoph

AU - Perkovic, Vlado

N1 - Copyright © 2020 The National Kidney Foundation, Inc and American Diabetes Association. Published by Elsevier Inc. All rights reserved.

PY - 2021

Y1 - 2021

N2 - Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to demonstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were observed. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio>300mg/g, and estimated glomerular filtration rate of 30 to<90mL/min/1.73m2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.

AB - Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to demonstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were observed. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio>300mg/g, and estimated glomerular filtration rate of 30 to<90mL/min/1.73m2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.

KW - Cardiovascular Diseases/epidemiology

KW - Diabetes Mellitus, Type 2/drug therapy

KW - Diabetic Nephropathies/metabolism

KW - Humans

KW - Protective Agents/pharmacology

KW - Research

KW - Risk Adjustment/methods

KW - Sodium-Glucose Transporter 2 Inhibitors/pharmacology

U2 - 10.1053/j.ajkd.2020.08.003

DO - 10.1053/j.ajkd.2020.08.003

M3 - Journal article

C2 - 33121838

VL - 77

SP - 94

EP - 109

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

IS - 1

ER -