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CV Benefits of SGLT-2 Inhibitors Extend Beyond High-risk Patients

Information sourced from NEJM Journal Watch:

How Broad Are the Benefits of SGLT-2 Inhibitors?

Compared with other agents, SGLT-2 inhibitors were associated with improved outcomes in real-world patients from 6 countries.

Clinical trials have shown that sodium-glucose cotransporter (SGLT-2) inhibitors significantly reduce adverse cardiovascular events, including death, in patients with type 2 diabetes (NEJM JW Cardiology Jan 2018 and Circulation 2018; 137:323). However, these trials have largely been limited to relatively high-risk populations in the U.S. and Europe. Using administrative data, the industry-funded CVD-REAL 2 investigators explored associations between SGLT-2 inhibitor initiation and cardiovascular outcomes in more than 400,000 patients in South Korea, Japan, Singapore, Israel, Australia, and Canada (NCT02993614).

A minority of participants had established cardiovascular disease (about 27%), and 45% were women. After propensity-score matching, initiation of an SGLT-2 inhibitor was associated with significant reductions in the risks for death (hazard ratio, 0.51), heart failure hospitalization (HR, 0.64), myocardial infarction (HR,0.81), and stroke (HR,0.68), compared with other glucose-lowering therapies. The results were directionally consistent across countries and among prespecified subgroups.


The results of this elegant epidemiological investigation suggest that the benefits of SGLT-2 inhibitors are likely a class effect and extend to lower-risk patients from diverse backgrounds. However, residual confounding — inherent in all observational studies — probably accounts in part for the magnitude of the observed effect. The researchers also did not examine the adverse effects of these drugs. As the authors discuss, the ongoing DECLARE-TIMI 58 clinical trial (NCT01730534) will provide more-definitive information about the benefits and risks of SGLT-2 inhibitors in lower-risk diabetic populations. In the meantime, clinicians can be reasonably confident about prescribing these agents in a wide range of patients with type 2 diabetes.

Fatima Rodriguez, MD, MPH reviewing Kosiborod M et al. J Am Coll Cardiol 2018 Mar 11.


Kosiborod M et al. Lower cardiovascular risk associated with SGLT-2i in >400,000 patients: The CVD-REAL 2 study. J Am Coll Cardiol 2018 Mar 11; [e-pub].

NEJM Journal Watch is produced by NEJM Group, a division of the Massachusetts Medical Society. Copyright ©2018 Massachusetts Medical Society. All rights reserved.

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