Objective: SGLT2 inhibitors (SGLT2i) were examined for their effects on nighttime sympathetic nerve activity in type 2 diabetic patients.

Methods: A total of 15 type 2 diabetic outpatients with poor glycemic and body weight control despite conventional antidiabetic therapy (HbA1c, 7.7 ± 1.1%; BMI, 27.6 ± 3.8 kg/m2) were given dapagliflozin (Dapa) 5 mg/day for 3 months. Patients were compared before and 3 months after Dapa treatment for Low frequency/High frequency (LF/HF) ratios at 5-minute intervals as index of sympathetic verve activity through spectrum analysis of heart rate variability, blood pressure (BP) variability at 30-minute intervals, glucose variability at 5-minute intervals using concurrent Holter electrocardiogram, ambulatory blood pressure monitoring, and continuous glucose monitoring. Blood samples were drawn from these patients after 30 minutes of bed rest before and 3 months after Dapa treatment to measure their plasma catecholamine values. Outcome measures of the study included the area under the curve for LF/HF ratios (AUC-LF/HF ratio), mean BP values during sleep, extent of nighttime BP dip, and mean glucose/SD of glucose values during sleep.

Results: HbA1c and body weight were significantly decreased with Dapa. Again, the nighttime AUC-LF/HF ratio and plasma noradrenalin values, as well as the heart rate, systolic BP (SBP) and diastolic BP (DBP) values during the same hours, were significantly decreased, and the extent of nighttime BP dip was also significantly increased, in those achieving weight reductions with Dapa. In contrast, these findings were not observed in 3 patients failing to achieve weight reductions with Dapa.

Conclusions: Study results suggest that reductions in sympathetic nerve activity associated with the SGLT2i treatment may be closely associated with SGLT2i-mediated weight reductions.


T. Onishi: None. Y. Shioda: None. Y. Mori: None.

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