Τίτλος:
Mechanisms for cardiorenal protection of sglt-2 inhibitors
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 cardio-and 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. © 2021 Bentham Science Publishers.
Συγγραφείς:
Georgianos, P.I.
Vaios, V.
Dounousi, E.
Salmas, M.
Eleftheriadis, T.
Liakopoulos, V.
Περιοδικό:
Current Pharmaceutical Design
Εκδότης:
Bentham Science Publishers
Λέξεις-κλειδιά:
canagliflozin; dapagliflozin; empagliflozin; ertugliflozin; glimepiride; glucose; hemoglobin A1c; hydrochlorothiazide; interleukin 1beta; losartan; messenger RNA; metformin; nucleotide binding oligomerization domain like receptor; placebo; sodium glucose cotransporter 2; sodium glucose cotransporter 2 inhibitor; uric acid; antidiabetic agent; sodium glucose cotransporter 2, albuminuria; antifibrotic activity; antiinflammatory activity; cardiovascular response; cardiovascular risk; diabetic nephropathy; diastolic blood pressure; disease exacerbation; dose response; down regulation; drug dose titration; drug efficacy; drug mechanism; estimated glomerular filtration rate; focal glomerulosclerosis; glucose blood level; glucose urine level; glycemic control; heart failure; heart protection; hemodynamics; hemoglobin blood level; human; kidney disease; kidney function; kidney plasma flow; non insulin dependent diabetes mellitus; outcome assessment; oxidative stress; priority journal; protein expression; renal protection; Review; risk reduction; systolic blood pressure; treatment duration; treatment outcome; vasoconstriction; cardiovascular system; complication; diabetic nephropathy; non insulin dependent diabetes mellitus; pharmacology, Cardiovascular System; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hypoglycemic Agents; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
DOI:
10.2174/1381612827666210119102409
