Physicians' Academy for Cardiovascular Education

Real-world data show clinical benefit of empagliflozin, which is likely a class effect

Lower Risk of Heart Failure and Death in Patients Initiated on SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study

Kosiborod M, Cavender MA, Fu AZ, et al. - Circulation 2017; published online ahead of print


Higher HbA1c levels are associated with an increased cardiovascular disease (CVD) risk, however intensive glucose control has not been related to a reduction of heart failure (HF) development and of cardiovascular (CV)- or all-cause death so far [1,2].

In the EMPA-REG OUTCOME study, there was a substantial reduction in CV death and hospitalization for heart failure (HHF) in type 2 diabetes mellitus (T2DM) patients with established atherosclerotic CVD, who were randomized to the SGLT-2 inhibitor empagliflozin [3,4]. There was only a small difference in HbA1c levels between empagliflozin- and placebo-treated patients, therefore the clinical benefit cannot be explained by glucose-lowering. Although mechanisms explaining the EMPA-REG OUTCOME study results are unclear, the question remains whether the clinical benefits related to SGLT-2 inhibitor treatment are reproducible in clinical practice.

In this real-world practice international study (6 countries), the risk for HHF, death and the combined endpoint of HHF or death was assessed in T2DM patients treated with SGLT-2 inhibitors (n=166,033) or with other glucose-lowering drugs (oGLDs, n=1,226,221). This was done to confirm the CV benefits with SGLT-2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) in real-world setting, to determine whether there is a class effect and to verify the effects in T2DM patients with a broader CV risk profile than this in the EMPA-REG OUTCOME study, which only included patients with established CVD.

Main results


In a large multinational study, treatment of T2DM patients with SGLT-2 inhibitors versus oGLDs was associated with lower rates of HHF and death in a real-world setting. Since the overwhelming majority of patients did not have established CVD, this suggests that the benefits of SGLT-2 inhibitors on the prevention of heart failure may extend to lower-risk patients than those enrolled in randomized trials so far. Moreover, as there is substantial variation in SGLT2 inhibitor use between geographic regions and no heterogeneity in results was observed across counties, this suggests that there is likely a class effect for SGLT-2 inhibitors.


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Find this article online at Circulation