Physicians' Academy for Cardiovascular Education

Three SGLT2 inhibitors associated with decreased CVD risk in real-world setting

Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic)

A multinational observational analysis

Literature - Birkeland KI, Jørgensen ME, Carstensen B, et al. - Lancet Diabetes Endocrinol 2017; epub ahead of print


Improving glucose control alone has not been shown to reduce the cardiovascular (CV) risk, however, SGLT2 inhibitors empagliflozin and canagliflozin have been associated with a convincing CV risk reduction [1-5]. It remains to be shown whether these effects will be seen for all SGLT2 inhibitors and whether these findings can be translated into real-world clinical settings.

In this study, it was evaluated whether new use of SGLT2 inhibitors compared with new use of other glucose-lowering drugs, were associated with changes in CV mortality and disease risk, including MACE and hospital events for heart failure (HF).

For this purpose, an observational analysis was performed based on national registry data from Denmark, Norway, and Sweden (CVD REAL). This included all patients with type 2 diabetes mellitus (T2DM) who started a new glucose-lowering drug after the introduction SGLT2 inhibitors (2012 or 2013) until the end of 2015 (n=435,629). Propensity scores (1:3) were used to match each patient who initiated an SGLT2 inhibitor (n=91,320) with patients who initiated other glucose-lowering drugs (n=68,490).

CV outcomes were CV mortality, MACE including CV mortality, myocardial infarction (MI) and ischemic or hemorrhagic stroke, hospital event for HF, non-fatal MI and non-fatal stroke. Other predefined outcomes were all-cause mortality, atrial fibrillation (AF) and severe hypoglycemia.

Main results


In a real-world clinical setting, new use of an SGLT2 inhibitor was associated with a decreased CVD and CV mortality risk compared with the new use of other glucose-lowering drugs in diabetic patients. This is consistent with results of CV outcome trials of drugs in this class. Moreover, as more than 90% of SGLT2 inhibitor exposure time was contributed by dapagliflozin, the finding lend support for a possible class effect, as findings were complementing to what has previously been shown in CV outcome trials with empagliflozin and canagliflozin. These findings could be useful for health-care practitioners treating diabetic patients at high CVD risk.


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Find this article online at Lancet Diabetes Endocrinol

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