The effect of sodium-glucose cotransporter-2 inhibitors on the cardiovascular system in patients under 65 years of age with diabetes mellitus and no history of cardiovascular disease

Objective: This study aimed to evaluate the early effects of SGLT-2 inhibitors on the autonomic nervous system and cardiovascular system in individuals under the age of 65 with type 2 diabetes mellitus and no known cardiovascular disease. Methods: Patients who received empagliflozin or dapagliflozin for three months were evaluated using 24-hour Holter monitoring (to assess heart rate variability and heart rate turbulence), speckle-tracking echocardiography, surface electrocardiography, and biochemical parameters. Results: A total of 52 patients were included in the study. The mean age was 53.04 years (range: 36–65), and 48.08% were male. Among the patients, 78.85% used empagliflozin (25 mg/day) and 21.15% used dapagliflozin (10 mg/day). The mean duration of diabetes was 3.64 years. After three months of treatment, SDANN (p=0.036) and LF power (p=0.020) significantly increased, while no significant change was observed in the LF/HF ratio (p=0.357). According to the 24-hour Holter analysis, the minimum heart rate decreased by 1.86 bpm (p=0.039). The mean heart rate measured by surface electrocardiography also showed a statistically significant reduction of 4.26 bpm (p=0.007). Significant reductions were observed in body weight (5.67±3.63 kg, p<0.001), body mass index (2.07±1.27 kg/m², p<0.001), and HbA1c levels (1.11%, p<0.001). Additionally, a significant increase of 0.06±0.18 mmol/L in serum magnesium levels was recorded (p=0.014). A significant improvement of 2.23±2.55 units in global longitudinal strain was noted (p<0.001). Electrocardiographic evaluations revealed significant prolongations in QT interval (16.23±21.42 ms, p<0.001), QTc Bazett (8.47±23.64 ms, p=0.012), QTc Fridericia (11.39±18.88 ms, p<0.001), and QTc Hodges (8.76±18.64 ms, p=0.001). Conclusion: SGLT-2 inhibitors demonstrated balancing and regulatory effects on the autonomic nervous system in diabetic patients and resulted in significant improvements in heart rate variability and left ventricular mechanical function. These findings suggest that such agents may offer a potential therapeutic option for the modulation of autonomic dysfunction. However, caution is warranted regarding the observed prolongations in QT and QTc intervals, which may indicate the need for additional monitoring during treatment.