Real world data suggest that CV benefit of SGLT-2 inhibitors applies in most world regions

Lower Risk of Cardiovascular Events and Death Associated with Initiation of SGLT-2 Inhibitors versus Other Glucose Lowering Drugs – Real World Data Across Three Major World Regions with More Than 400,000 Patients: The CVD-REAL 2 Study

News - Mar. 12, 2018

Introduction and methods

Outcome trials have shown a lower risk of CV events upon treatment with sodium glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2DM), most of whom had established CV disease (CVD). CVD-REAL was a large, international pharmaco-epidemiologic study that demonstrated that SGLT-2i were associated with similar CV effects, across compounds, and in a much broader population of patients with T2DM seen in clinical practice, as compared with the outcome trials. Those analyses did, however, focus on all-cause death and heart failure (HF). Moreover, they only included patients from the USA and Europe, although most patients with T2DM reside outside these regions, in Asia-Pacific and the Middle East. Patient characteristics, treatment patterns and types of adverse CVD events vary among world regions, but well-designed comparative effectiveness studies evaluating CV outcomes with antidiabetic therapies are sparse outside the USA and Europe.

The CVD-REAL 2 study therefore aimed to evaluate the relationship between the initiation of SGLT-2i as compared with other glucose-lowering drugs (GLD) and a broad range of CV outcomes (all-cause death, hospitalization for HF (HHF), myocardial infarction (MI) and stroke) in patients with T2DM from three major regions: Asia-Pacific, Middle-East and North-America. 235064 patients on SGLT-2i were propensity matched with patients on GLD (mean age 57 years old).

Main results

  • Across all regions, SGLT-2i showed a lower rate of all-cause death than GLD (HR: 0.51, 95%CI: 0.37-0.70, P<0.001, n=442686).
  • Differences in the treatment effect on all-cause death were seen across regions, with the largest effect of SGLT-2i seen in Australia (HR: 0.32, 95%CI: 0.27-0.38, n=27442), and the smallest in Korea (HR: 0.72, 95%CI: 0.67-0.77, n=336644). In Singapore, the effect was non-significant (HR: 0.75, 95%CI:- 0.38-1.47, n=2726).
  • Overall, SGLT-2i was associated with a lower risk of HHF (HR: 0.64, 95%CI: 0.50-0.82, P=0.001). The treatment effect on HHF varied between Canada (HR: 0.36, 95%CI: 0.24-0.56, n=16064) and Korea (HR: 0.87, 95%CI: 0.82-0.92).
  • Overall, SGLT-2i was associated with a lower risk of MI (HR: 0.81, 95%CI: 0.74-0.88, P<0.001), but only Korea showed a 95%CI that excluded 1 (HR: 0.81, 95%CI: 0.74-0.89).
  • Overall, SGLT-2i was associated with a lower risk of stroke (HR: 0.68, 95%CI: 0.55-0.84), with more variation in the 95%CI’s.
  • Subgroup analyses based on specific CVD manifestations at baseline did not show significant interactions with the treatment effect of SGLT-2i.


This large, international study conducted in three major world regions, in over 400000 patients showed that initiation of SGLT-2i in patients with T2DM, as compared with GLDs, was associated with a lower risk of death, HHF, MI and stroke. Although specific effects varied across regions, the directionality of the associations was generally consistent across countries. These findings suggest that the CV effects of SGLT-2i may extend across patient ethnic and racial backgrounds, geographic regions as well as the CV risk continuum.


Our coverage of ACC.18 is based on the information provided during the congress.

This study was published simultaneously in JACC

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