SGLT-2 Inhibitors Linked to Lowered Risk of Mortality, MI, Stroke, and Hospitalization for Heart Failure

MARCH 11, 2018
Matt Hoffman
Mikhail Kosiborod, MD
Initiating SGLT-2 inhibition therapy is associated with a lower risk of death, hospitalization for heart failure (HHF), myocardial infarction (MI), and stroke compared to other glucose-lowering drugs (oGLDs) in patients with type 2 diabetes.

The multicenter, real-world study, CVD-REAL 2, included data from 470,128 patients matched 1:1 to either SLGT-2 inhibitors (n = 235,064) or oGLDs, and was presented at the 67th American College of Cardiology Scientific Sessions in Orlando, Florida, by Mikhail Kosiborod, MD, a cardiologist and clinical researcher at St. Luke’s Mid America Heart Institute, and a professor of medicine at the University of Kansas-Missouri-Kansas City.

“These findings suggest that the cardiovascular effects of SGLT-2 inhibitors may extend across patient ethnic and racial backgrounds, geographic regions, as well as the CV risk continuum,” Kosiborod said. The data centers were based in Australia (n = 27,442), Canada (n = 16,064), Israel (n = 19,472), Japan (n = 67,780), Singapore (n = 2726), and South Korea (n = 336,644).

The use of SGLT-2 inhibitors was broken down, with 75% of patients on dapagliflozin, 9% on empagliflozin, 8% on ipragliflozin (in South Korea and Japan, only), 4% on canagliflozin, 3% on tofogliflozin, and 1% on luseogliflozin (in Japan only).

The results showed that overall when compared with oGLDs, SGLT-2 inhibition use was associated with a hazard ratio (HR) of 0.51 for all-cause death (95% CI, 0.37–0.70; P <.001), 0.64 for HHF (95% CI, 0.50–0.82; P = .001), 0.81 for MI (95% CI, 0.75–0.88; P <.001), and 0.68 for stroke (95% CI, 0.55–0.84; P <.001).

Additionally, for the composite of all-cause death or HHF, the HR for SGLT-2 inhibitors was 0.60 (95% CI, 0.47–0.76; P <.001).

“The directionality of these associations was generally consistent across countries,” Kosiborod said. “The results were stable in multiple sensitivity analyses and across patient subgroups.”

The subgroup analyses showed that all-cause death (0.70 vs. 1.98), heart failure (0.60 vs. 3.73), MI (0.30 vs. 1.15), stroke (0.74 vs. 3.73), and the composite of all-cause death and HHF (1.23 vs. 5.31) had lower event rates in the SGLT-2 inhibition arm than the oGLDs arm.

There were limitations to the study, most notably that safety data was not examined, and there is a possibility that the residual, unmeasured confounding data cannot be definitively excluded from the analysis.


While mortality data was only available from inpatient settings in the instance of Japan and Singapore, Kosiborod justified the finding, saying that “most of the fatal events in these countries occur in the hospital.” Additionally, the sensitivity analyses excluding these 2 locales produced similar findings.

“SGLT-2 inhibition experience in real-world practice is still relatively short,” Kosiborod said, “and longer-term follow-up will be required to examine whether these effects are sustained over time.”

The study, “Lower Cardiovascular Risk Associated with SGLT-2i in >400,000 Patients: The CVD-REAL 2 Study,” was simultaneously published in the Journal of the American College of Cardiology.

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