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Type 2 diabetes and the kidney: insights from cardiovascular outcome trials

Dario Giugliano, Luca De Nicola, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
Diabetes, Obesity & Metabolism 2019 April 10
Diabetic kidney disease (DKD) still remains a progressive condition that is associated with higher risk of end-stage kidney disease and significant cardiovascular morbidity and mortality. Twelve cardiovascular outcome trials (CVOTs) in type 2 diabetes (T2D) have been so far published. Most trials with dipeptidyl-peptidase inhibitors (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin, and CARMELINA with linagliptin), and with the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (ELIXA with lixisenatide, LEADER with liraglutide, SUSTAIN-6 with semaglutide, EXCSEL with exenatide once weekly, and HARMONY with albiglutide) pointed toward reduced albuminuria which is a surrogate endpoint possibly heralding renal function preservation. The three trials with the sodium glucose co-transporter 2 inhibitors (SGLT-2i, empagliflozin, canagliflozin and dapagliflozin) also demonstrated a salutary effect on long-term eGFR, suggesting that SGLT-2i are more effective at mitigating loss of kidney function than are incretin-based therapies; moreover, SGLT-2i also have the advantage of plausible haemodynamic mechanisms for improved renal outcomes. Despite some residual limitations linked to differences in study populations and patient characteristics, the cardiorenal protective actions of SGLT-2 inhibitors, and to a lesser extent by some GLP-1 agonists, make them favorable medications for patients with T2D at increased cardiorenal risk. There is room for optimism that their use may change the paradigm of the ineluctable progression of DKD. This article is protected by copyright. All rights reserved.


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