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

• Published in: Diabetic medicine 2017-10, Vol.34 (10), p.1367-1371
• Main Authors: Sato, T., Miki, T., Ohnishi, H., Yamashita, T., Takada, A., Yano, T., Tanno, M., Tsuchida, A., Miura, T.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arrhythmia; Blood pressure; Body weight; Cardiac arrhythmia; Cardiovascular diseases; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetic Angiopathies - drug therapy; Electrocardiography; Female; Glucose; Glucose transporter; Health risk assessment; Heart diseases; Heart rate; Heart Rate - drug effects; Humans; Hypoglycemic Agents - therapeutic use; Male; Middle Aged; Mortality; Retrospective Studies; Sodium; Sodium-Glucose Transporter 2 - antagonists & inhibitors; Treatment Outcome; Ventricle; Ventricular Dysfunction - drug therapy; Ventricular Dysfunction - etiology
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/dme.13424

Aims To test the hypothesis that treatment with a sodium‐glucose co‐transporter‐2 inhibitor would reverse ventricular repolarization heterogeneity, a predictor of cardiovascular mortality, in people with Type 2 diabetes. Methods We retrospectively analysed changes in indices of ventricular repolarization before and after treatment with a sodium‐glucose co‐transporter‐2 inhibitor in 46 people with Type 2 diabetes. Results Sodium‐glucose co‐transporter‐2 inhibitor treatment reduced HbA1c concentration [62±13 mmol/mol (7.7±1.2%) vs 59±16 mmol/mol (7.5±1.4%)], body weight (77.8±13.9 vs 74.7±12.5 kg) and systolic blood pressure (133±18 vs 126±12 mmHg) in the study participants. Heart rate and QTc interval were not changed by sodium‐glucose co‐transporter‐2 inhibitor treatment, but QTc dispersion was significantly reduced (median, 48.8 vs 44.2 ms). Sodium‐glucose co‐transporter‐2 inhibitor treatment reversed QTc dispersion more in participants who had larger QTc dispersion before the treatment. Changes in systolic blood pressure (Spearman's ρ= 0.319; P=0.031), but not in HbA1c concentration, were correlated with changes in QTc dispersion after sodium‐glucose co‐transporter‐2 inhibitor treatment. Conclusions 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. What's new? In this study, we found that treatment with a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor reduced prolonged QTc dispersion in people with Type 2 diabetes, independently of its effect on glycaemic control. Because increased repolarization heterogeneity is associated with fatal arrhythmia and sudden cardiac death, these results suggest that improvement in ventricular repolarization heterogeneity is one of the mechanisms by which SGLT2 inhibitor treatment reduced mortality in the EMPA‐REG OUTCOME trial.