Title:Mechanisms for Cardiorenal Protection of SGLT-2 Inhibitors
Volume: 27
Issue: 8
Author(s): Panagiotis I. Georgianos, Vasilios Vaios, Evangelia Dounousi, Marios Salmas, Theodoros Eleftheriadis and Vassilios Liakopoulos*
Affiliation:
- Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki,Greece
Keywords:
Cardiorenal protection, clinical outcomes, diabetic kidney disease, sodium-glucose co-transporter 2 inhibitors, blood pressure,
renin-angiotensin-system (RAS).
Abstract: Despite optimal treatment of diabetic kidney disease (DKD) with adequate blood pressure control
and agents blocking the renin-angiotensin-system (RAS), the residual cardiorenal risk of these patients remains
substantially high. There is, therefore, an unmet need for additional therapies effective to retard the progression
of DKD and improve cardiovascular outcomes in this high-risk population. Sodium-glucose co-transporter 2
(SGLT-2) inhibitors represent a novel drug class that received regulatory approval for improving glycemic control
in patients with type 2 diabetes and preserved kidney function. Large outcome trials designed to test their
cardiovascular safety profile showed an unexpected improvement in cardiovascular outcomes and also suggested
a slower progression of DKD with SGLT-2 inhibition. The Canagliflozin and Renal Outcomes in Type 2 Diabetes
and Nephropathy (CREDENCE), a trial that was designed to specifically investigate the renoprotective
properties of SGLT-2 inhibitors in patients with overt DKD already receiving guideline-based therapy with a
RAS-blocker, was prematurely terminated due to an impressive benefit of canagliflozin on kidney and cardiovascular
outcomes. These impressive results refine the role and the indication of SGLT-2 inhibitors as a cardioand
renoprotective strategy in patients with DKD. In this article, we provide an overview of the available clinical-
trial evidence and explore the mechanisms mediating the cardiorenal protection afforded by SGLT-2 inhibitors.
We conclude with perspectives for a potential beneficial effect of this novel drug class in patients with
non-diabetic kidney disease.
