The cardiovascular benefits of empagliflozin: SGLT2-dependent and -independent effects

Excerpt

In the EMPA-REG OUTCOME trial, therapy with the sodium/glucose co-transporter (SGLT) 2 inhibitor empagliflozin over just 2.6 years was associated with a 14% reduction in the risk of major cardiovascular events, driven by a marked and unexpected reduction in cardiovascular mortality (38%) in patients with type 2 diabetes and established cardiovascular disease [1]. The drug also reduced the incidence of heart failure hospitalisation (HFH) by 35%. The magnitude of these benefits and their rapid emergence after only a few months from randomisation make it unlikely that the modest benefits on HbA_1c (−0.4% compared with placebo), body weight (−2 kg) and systolic/diastolic blood pressure (4/2 mmHg) were responsible [1]. Moreover, the divergence in the HRs for non-fatal myocardial infarction (HR 0.87 [95% CI 0.70, 1.09]) vs non-fatal stroke (HR 1.24 [0.92, 1.67]) makes it unlikely that the benefits of empagliflozin involved classical effects on atherosclerosis. Accordingly, additional mechanisms and mediators need to be considered to better understand why empagliflozin had such important benefits in this trial [2‐5]. …