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Diabetes Metab Syndr Obes. 2018 Apr 12;11:133-148. doi: 10.2147/DMSO.S154602. eCollection 2018.

Cardiovascular effects of sodium glucose cotransporter 2 inhibitors.

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Division of Endocrinology and Metabolism, University of California San Diego, San Diego, CA, USA.


As the first cardiovascular (CV) outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM), the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME®) trial, which investigated the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL), which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM.


canagliflozin; cardiovascular outcomes; dapagliflozin; empagliflozin; mechanisms; sodium glucose cotransporter 2 inhibitors

Conflict of interest statement

Disclosure T.S.C. receives speaker’s bureau and/or consultant fees from Dexcom, Sanofi, Novo Nordisk, and Valeritas. J.P. receives speaker’s bureau fees and consulting fees from Insulet, Sanofi, and Valeritas, and consulting fees from Dexcom, MannKind, and Novo Nordisk. Medical writing assistance, supported financially by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI), was provided by Geraldine Thompson, PhD, Jennifer Garrett, MB BS, and Debra Brocksmith, MB ChB, PhD, of Envision Scientific Solutions during the preparation of this manuscript. BIPI was given the opportunity to review the data used in the manuscript for factual accuracy only. The authors report no other conflicts of interest in this work.

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