Effect of sodium‐glucose co‐transporter‐2 inhibitors on impaired ventricular repolarization in people with Type 2 diabetes

Abstract

The findings suggest that sodium-glucose co-transporter-2 inhibitor treatment reverses ventricular repolarization heterogeneity in people with Type 2 diabetes, independently of its effect on glycaemic control. The favourable effect on ventricular repolarization heterogeneity could be the mechanism by which empaglifozin reduced cardiovascular events in a recent study.

Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials

“…A retrospective study by Sato et al examined 46 patients with T2DM and reported that treatment with SGLT2 inhibitors decreased previously increased Q‐Td in these patients by roughly 9%, a finding independent of glucose control and correlated with a reduction in blood pressure. Patients with T2DM within the low dispersion of Q‐Tc (Q‐Tcd) subgroup (normal range as defined by >37 milliseconds) did not benefit as much from SGLT2 inhibition . These findings indicate that SGLT2 inhibitors have promising effects on ventricular repolarization that support a potential anti‐arrhythmic effect not previously seen, a probable attributable factor in the mortality benefit seen with empagliflozin in the EMPA‐REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study .…”

“…Patients with T2DM within the low dispersion of Q‐Tc (Q‐Tcd) subgroup (normal range as defined by >37 milliseconds) did not benefit as much from SGLT2 inhibition . These findings indicate that SGLT2 inhibitors have promising effects on ventricular repolarization that support a potential anti‐arrhythmic effect not previously seen, a probable attributable factor in the mortality benefit seen with empagliflozin in the EMPA‐REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study . Most patients with hypertension in the EMPA‐REG OUTCOME trial had increased left ventricular mass defined by ECG findings, a possible cause of increased Q‐Td believed to be due myocardial hypertrophy warranting increased repolarization .…”

“…It is a well‐known noninvasive measurement to quantify variation in ventricular repolarization and can act as a marker of myocardial electrical stability . Patients with T2DM have shown to have greater Q‐T interval (QTc) dispersion than patients without diabetes . This is attributed to the autonomic neuropathy seen in patients with T2DM and resulting neurological dysregulation of the myocardium, compromising cardiac electromechanical coupling.…”

“…Most patients with hypertension in the EMPA‐REG OUTCOME trial had increased left ventricular mass defined by ECG findings, a possible cause of increased Q‐Td believed to be due myocardial hypertrophy warranting increased repolarization . It is hypothesized that the stable Q‐Td and reduced repolarization heterogeneity (and thus, sudden cardiac death) seen in the EMPA‐REG OUTCOME trial was one mechanism by which CV death was decreased in patients taking empagliflozin …”

Comparative effectiveness of cardiovascular outcomes in new users of sodium-glucose cotransporter-2 inhibitors: SGLT2 inhibitors in the real world

“…One study has shown that SGLT-2 inhibitors have favourable effects on ventricular repolarization heterogeneity which has previously been shown to be a predictor of CV mortality in T2DM (12). Furthermore, it has been suggested that SGLT-2 inhibitors may play a role in modulating sympathetic tone as the volume contraction induced by this class of medication is not accompanied by an increase in pulse rate.…”