Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Sympathetic Nervous System Activity Detected by Sympathetic Activity Index and LF/HF Ratio in Patients with Type 2 Diabetes Mellitus

Abstract

Objective: Cardiac autonomic neuropathy is a serious microvascular complication of type 2 diabetes mellitus that affects a significant portion of patients. Due to decreased parasympathetic activity, the sympathetic nervous system becomes dominant, causing several problems that lead to increased cardiovascular morbidity and mortality. Sodium-glucose cotransporter-2 inhibitors have been shown to reduce sympathetic nervous system activity previously. This is a promising finding for restoring the impaired sympathovagal balance in cardiac autonomic neuropathy. The aim of this study is to evaluate the effect of at least 6 months of sodium-glucose cotransporter-2 inhibitor treatment on sympathetic nervous system activity with sympathetic activity index and heart rate variability parameters in patients with type 2 diabetes mellitus.

Methods: Holter-electrocardiogram recordings of 50 patients who were using an sodiumglucose cotransporter-2 inhibitor (empagliflozin or dapagliflozin) for at least 6 months and 50 patients who did not were analyzed retrospectively. The sympathetic activity index and heart rate variability parameters of these 2 groups, which were similar in terms of age, gender, hemoglobin A1c, and duration of diabetes, were compared.

Results: The ratio of low-frequency to high-frequency power reflecting the sympathovagal balance [-1.495 (-2.165/-1.196) vs. -1.224 (-1.619/-0.863), P=.008] and sympathetic activity index [1.44 (1.06/2.76) vs. 2.47 (1.42/3.68), P=.009] was lower in the sodiumglucose cotransporter-2 inhibitor group than in the control group. In addition, the sympathetic activity index was correlated with the ratio of low-frequency to high-frequency power (r=0.418, P < .001).

Conclusion: Sodium-glucose cotransporter-2 inhibitor treatment for at least 6 months was found to result in lower values of sympathetic activity index and the ratio of low-frequency to high-frequency power in patients with type 2 diabetes mellitus. These findings indicate lower sympathetic nervous system activity, which supports the sympathoinhibitor effects of sodiumglucose cotransporter-2 inhibitors.