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Effects of SGLT2 Inhibitors as an Add-on Therapy to Metformin on Electrocardiographic Indices of Ventricular Repolarization.

Background
According to EMPA-REG OUTCOME, trial use of empagliflozin in patients with a history of cardiovascular disease improves hospitalization for heart failure and decreases cardiovascular morbidity and mortality. Recent studies have shown that a prolonged T-peak to T-end interval on the resting electrocardiography is associated with an increased risk of cardiovascular mortality. Tp-e/corrected QT interval (QTc) ratio is a reliable index of prolonged ventricular repolarization.


Objectives
In this study, we examined the effects of sodium glucose co-transporters 2 (SGLT2) inhibitors as an add-on therapy to metformin on electrocardiographic indices of ventricular repolarization.


Methods
Electrocardiographic recordings before combination therapy along with three months and six months follow-up of 141 consecutive patients who were switched from monotherapy to combination therapy with two oral agents due to inadequate glycemic control were derived. QT interval (QT), QTc, Tp-e intervals and Tp-e/QT, Tp-e/QTc ratios were calculated and analyzed.


Results
After the six month follow-up, there was a significant decrease in the QT interval in patients who were using SGLT2 inhibitors as an add-on therapy to metformin compared to other glucose-lowering agents (373.4 ± 9.9 ms vs. 385.4 ± 12.5 ms, 382.9 ± 11.2 ms; p < 0.001 respectively). Furthermore, Tp-e/QT and Tp-e/QTc ratios were significantly lower in this patient population compared to control groups (0.186 ± 0.023 vs. 0.196 ± 0.021, 0.191 ± 0.017; p < 0.001 and 0.174 ± 0.021 vs. 0.199 ± 0.022, 0.195 ± 0.016; p < 0.001 respectively).


Conclusions
Our data showed that using SGLT2 inhibitors as an add-on therapy to metformin favorably alters ventricular repolarization indices in patients with type 2 diabetes mellitus.