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Reference: Sattar, N, McLaren, J, Kristensen, SL et al., (2016). SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?. Diabetologia.Citable link to this page:

 

SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?

Abstract: While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30-40% reductions in heart failure hospitalisation, cardiovascular and all-cause deaths on empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular end-point trials for new diabetes agents were required and describe the results of the first four such trials to have reported as a precursor to understanding why EMPA-REG Outcomes results came as a surprise. Thereafter, we discuss potential mechanisms that could explain the EMPA-REG Outcomes results, concentrating on non-atherothrombotic effects. We suggest that the main driver of benefit may derive from the specific impact of SGLT2 inhibition on renal sodium and glucose handling, leading to both diuresis and to improvements in diabetes-related maladaptive renal arteriolar responses, effects which are likely to be beneficial in patients with clinical or subclinical cardiac dysfunction. The net result of these processes, we argue, is an improvement in cardiac systolic and diastolic function, thereby lowering risks of heart failure hospitalisation and sudden cardiac death. We also discuss whether other drugs in this class are likely to show similar cardiovascular benefits. Finally, areas for future research are suggested to better understand the relevant mechanisms and to identify other groups who may benefit from SGLT2 inhibitor therapy.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Accepted manuscriptNotes:© The Author(s) 2016 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Bibliographic Details

Publisher: Springer

Publisher Website: http://www.springer.com/

Journal: Diabetologiasee more from them

Publication Website: http://link.springer.com/journal/125

Issue Date: 2016-04Identifiers

Urn: uuid:fc6c809f-50df-42dc-b1f8-99ec9340de42

Source identifier: 618078

Eissn: 1432-0428

Doi: https://doi.org/10.1007/s00125-016-3956-x

Issn: 0012-186X Item Description

Type: Journal article;

Version: Accepted manuscriptKeywords: Blood pressure Cardiovascular mortality Empagliflozin Haemodynamic Heart failure Renal dysfunction Review Sodium-glucose linked transporter-2 Type 2 diabetes Tiny URL: pubs:618078

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Author: Sattar, N - - - McLaren, J - - - Kristensen, SL - - - Preiss, D - institutionUniversity of Oxford Oxford, MSD, Nuffield Departmen

Source: https://ora.ox.ac.uk/objects/uuid:fc6c809f-50df-42dc-b1f8-99ec9340de42



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