Renal protection: a leading mechanism for cardiovascular benefit in patients treated with SGLT2 inhibitors
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Renal protection: a leading mechanism for cardiovascular benefit in patients treated with SGLT2 inhibitors Davide Margonato 1,2 & Giuseppe Galati 3 & Simone Mazzetti 1 & Rosa Cannistraci 4 & Gianluca Perseghin 4 & Alberto Margonato 3 & Andrea Mortara 1 Accepted: 31 August 2020 # The Author(s) 2020
Abstract Initially developed as glucose-lowering drugs, sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have demonstrated to be effective agents for the risk reduction of cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM). Subsequently, data has emerged showing a significant CV benefit in patients treated with SGLT2i regardless of diabetes status. Renal protection has been initially evaluated in CV randomized trials only as secondary endpoints; nonetheless, the positive results gained have rapidly led to the evaluation of nephroprotection as primary outcome in the CREDENCE trial. Different renal and vascular mechanisms can account for the CV and renal benefits enlightened in recent literature. As clinical guidelines rapidly evolve and the role of SGLT2i appears to become pivotal for CV, T2DM, and kidney disease management, in this review, we analyze the renal effects of SGLT2, the benefits derived from its inhibition, and how this may result in the multiple CV and renal benefits evidenced in recent clinical trials. Keywords SGLT2 inhibitors . Chronic kidney disease . Type 2 diabetes mellitus . Renal protection . Cardiovascular outcomes . Heart failure
Introduction Sodium-glucose co-transporter type 2 inhibitors (SGLT2i) were originally developed to reduce hyperglycemia in diabetic patients via an insulin-independent mechanism, through their glycosuric effect. However, over the past 5 years, evidence from randomized clinical trials (RCTs) showed an unexpected benefit and safety in most cardiovascular (CV) and renal outcomes, irrespective on their impact on glycemic control.
* Davide Margonato [email protected] 1
Heart Failure Unit and Department of Cardiology, Policlinico di Monza, Via Amati 111, 20900 Monza, Italy
2
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
3
Heart Failure Unit and Department of Cardiology, San Raffaele Hospital and Scientific Institute (IRCCS), Milan, Italy
4
Department of Medicine and Surgery, Università Degli Studi di Milano Bicocca, & Policlinico di Monza, Monza, Italy
Chronic kidney disease (CKD) occurs in approximately 40% type 2 diabetes mellitus (T2DM) patients [1] and is associated with a very high risk of CV diseases [2]. Moreover, heart failure (HF) and CKD frequently coexist, sharing diabetes as one of the main risk factors, thus interacting in a vicious circle which contributes to a poor prognosis [3]. The growing evidence from many RCTs on SGLT2i as a CV protective class of drugs led to a class 1 level A recommendation for their use in patients with T2DM and established atherosclerotic CV disease (ACVD), or in patients with T2DM and multiple risk factors but without an ACVD [4]. More recently, SGLT2i showed t
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