SGLT-2 inhibitors on cardiac autonomic function in individuals with and without type 2 diabetes mellitus

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have emerged as key therapeutic agents in managing type 2 diabetes mellitus (T2DM) and obesity, offering benefits that extend beyond glycemic control. This review examines the role of SGLT-2 inhibitors in modulating cardiac autonomic function, with a particular focus on heart rate variability (HRV) as a biomarker of autonomic balance. These agents improve metabolic profiles through enhanced glucosuria, natriuresis, and weight loss, while concurrently reducing blood pressure. Importantly, they also attenuate sympathetic nervous system overactivity and promote parasympathetic modulation, which may lower the risk of adverse cardiovascular events. The underlying mechanisms include not only the metabolic effects but also anti-inflammatory and antioxidative actions, which together contribute to improved endothelial function and vascular health. Advanced HRV analyses, encompassing traditional time and frequency domain methods as well as nonlinear approaches, have proven valuable in detecting early autonomic dysfunction in high-risk populations. Some studies suggest that SGLT-2 inhibitors may be associated with improvements in HRV parameters, such as increased SDNN and RMSSD and a reduced LF/HF ratio. However, findings are inconsistent across studies, and further research is needed to determine the extent and mechanisms of these potential effects. Although these findings are promising, further standardized, long-term studies are essential to clarify the mechanisms and optimal therapeutic strategies involving SGLT-2 inhibitors in the management of autonomic dysfunction. Future research should also explore the synergistic potential of combining SGLT-2 inhibitors with other cardiometabolic therapies to enhance cardiovascular outcomes in individuals with and without T2DM.