Impact of sodium-glucose co-transporter inhibitors on cardiac autonomic function and mortality: no time to die

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to improve cardiovascular outcomes not only in patients with diabetes but also in those with heart failure, irrespective of diabetic status. However, the mechanisms underlying the cardioprotective effects of these newer anti-diabetic drugs remain to be fully elucidated. One exciting avenue that has been recently explored in both preclinical and clinical studies is the modulation of the cardiovascular autonomic nervous system. A reduction in sympathetic nervous system activity by SGLT2 inhibitors may potentially translate into a reduction in arrhythmic risk and sudden arrhythmic death, which may explain, at least partly, the cardioprotection shown in the cardiovascular outcome trials with different SGLT2 inhibitors. Although some of the data from the preclinical and clinical studies are promising, overall the findings can be contradictory. This highlights the need for more studies to address gaps in our knowledge of these novel drugs. The present review offers an in depth overview of the existing literature regarding the role of SGLT2 inhibitors in modulating cardiovascular autonomic function as one of the possible pathways of their cardioprotective effects.