SGLT-2 Inhibitors and Cardiovascular Risk

Study Questions:

What is the association between initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and heart failure (HF)/death in patients with/without cardiovascular disease (CVD)?


The investigators conducted the CVD-REAL study, a multinational, observational study in which adults with type 2 diabetes (T2D) were identified. Patients prescribed a SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of a SGLT-2i. The primary endpoints of interest were the time to death, HF, and the composite endpoint of HF or death. Hazard ratios (HRs) for the risk of death, HF, and HF/death in patients with and without established CVD were estimated for each country and pooled.


After propensity-score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with other GLDs, initiation of a SGLT-2i was associated with lower risk of death in patients with and without CVD (HR, 0.56; 95% confidence interval [CI], 0.44-0.70; HR, 0.56; 95% CI, 0.50-0.63). There was also an association between SGLT-2i and lower risk of HF (HR, 0.72; 95% CI, 0.63-0.82; HR, 0.61; 95% CI, 0.48-0.78) and the composite of HF or death (HR, 0.63; 95% CI, 0.57-0.70; HR, 0.56; 95% CI, 0.50-0.62) observed in patients with and without established CVD.


The authors concluded that initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD.


This observational analysis of the CVD-REAL study reports an association between the use of SGLT-2i and a lower risk of death and HF that was observed across the spectrum of risk including patients with and without established CVD. While long-term follow-up data from CVD-REAL and ongoing randomized clinical trials are needed to fully understand whether the effects of SGLT-2i are sustained over time, the current findings suggest that the CV benefits of SGLT-2i are a class effect, and may extend to a broader population of patients with T2D and with and without CVD. Data from ongoing randomized clinical trials will provide further insight regarding the CV benefits of different SGLT-2i including in patients without established CVD. Based on available data, SGLT-2i agents should be considered among the first-line agents in patients with T2D.

Keywords: Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glucose, Heart Failure, Ischemia, Metabolic Syndrome, Primary Prevention, Risk Factors, Sodium-Glucose Transporter 2

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