American College of Cardiology
American College of Cardiology
March 16, 2018
3 min read

CVD-REAL 2: SGLT2 inhibitors associated with lower risk for CV events, death in type 2 diabetes

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Mikhail N. Kosiborod, MD
Mikhail Kosiborod

ORLANDO, Fla. — Patients with type 2 diabetes who were treated with sodium-glucose cotransporter 2 inhibitors had a lower risk for HF hospitalization, death, stroke and MI compared with those who were treated with other glucose-lowering drugs, according to data from featured clinical research presented at the American College of Cardiology Scientific Session.

“The directionality of associations was generally consistent across countries, and results were stable in multiple sensitivity analyses and across patient subgroups,” Mikhail Kosiborod, MD, cardiologist at Saint Luke’s Mid America Heart Institute and professor of medicine at University of Missouri-Kansas City School of Medicine, said during the presentation.

As Cardiology Today previously reported, the first CVD-REAL study found that patients with diabetes treated with a SGLT2 inhibitor had lower rates of HF and death compared with other glucose-lowering drugs. That study only included patients from Europe and United States.

In CVD-REAL 2, researchers analyzed data from 470,128 episodes of treatment initiation from patients with established type 2 diabetes, either reflecting new use of SGLT2 inhibitors (n = 235,064; mean age, 57 years; 45% women; 27% with established CVD) or other glucose-lowering drugs (n = 235,064; mean age, 57 years; 46% women; 26% with established CVD). Patients were from North America, the Middle East and Asia-Pacific regions. Those with gestational diabetes or type 1 diabetes were excluded from the study.

Outcomes of interest included hospitalization for HF, all-cause death, MI, stroke and a composite of all-cause death or hospitalization for HF.

At baseline, about two-thirds of patients were treated with antihypertensive therapies and more than 50% of patients were on ACE inhibitors or angiotensin II receptor antagonists. Two-thirds of patients were also taking statin therapy. Metformin was used by about three-fourths of the cohort, while sulfonureyas and dipeptyl-peptidase IV inhibitors were used by slightly more than half.

Six different types of SGLT2 inhibitors were used during the study, with 75% of patients taking dapagliflozin (Farxiga, AstraZeneca).

During follow-up, all-cause death occurred in 5,216 patients and hospitalization for HF occurred in 5,997 patients. Compared with the other glucose-lowering drug group, the SGLT2 inhibitor group had a lower associated risk for all-cause death (HR = 0.51; 95% CI, 0.37-0.7) and hospitalization for HF (HR = 0.64; 95% CI, 0.5-0.82). The benefit for all-cause death and HF hospitalization associated with SGLT2 inhibitor initiation was also statistically significant in all individual participating countries except Singapore; HF hospitalization data were not available for Australia.

For the composite of all-cause death or HF hospitalization, 9,788 events occurred. Initiation of SGLT2 inhibitors was associated with a lower risk for the composite endpoint vs. other glucose-lowering drugs (HR = 0.6; 95% CI, 0.47-0.76), and this was also statistically significant in all individual participating countries for which complete data were available, Kosiborod said.

The risk for MI was modestly lower with SGLT2 inhibitors compared with other glucose-lowering drugs (HR = 0.81; 95% CI, 0.74-0.88). A significantly lower risk for stroke was also seen in this group (HR = 0.68; 95% CI, 0.55-0.84).

In subgroup analyses, event rates were higher in patients with established CVD compared with those without established CVD at baseline. Risk reductions associated with SGLT2 inhibitors compared with other glucose-lowering drugs were consistent in patients with and without prior CVD.

“Collectively, these findings suggest that the cardiovascular effects of SGLT2 inhibitors may extend across patient ethic and racial backgrounds, geographic regions, as well as cardiovascular risk continuum,” Kosiborod said.

Results from this study have also been published in the Journal of the American College of Cardiology. – by Darlene Dobkowski


Kosiborod M, et al. Featured Clinical Research II: Interventional. Presented at: American College of Cardiology Scientific Session; March 10-12, 2018; Orlando, Fla.

Kosiborod M, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.03.009.

Disclosures: The study was supported by AstraZeneca. Kosiborod reports he receives consultant fees/honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen Pharmaceuticals, Merck, Novartis, Novo Nordisk, Sanofi-Aventis and ZS Pharma; and research support from AstraZeneca and Boehringer Ingelheim.