Özel Hasan Fehmi, Alpay Şüheda, Asker Emre, Gültekin Elif Sıdal, Kazdağlı Hasan
Vocational School of Health Services, Manisa Celal Bayar University, Manisa, Türkiye.
Physiology Dept., Faculty of Medicine, Manisa Celal Bayar University, Manisa, Türkiye.
J Diabetes Complications. 2025 May;39(5):109021. doi: 10.1016/j.jdiacomp.2025.109021. Epub 2025 Mar 27.
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.
钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂已成为治疗2型糖尿病（T2DM）和肥胖症的关键治疗药物，其益处不仅限于血糖控制。本综述探讨了SGLT-2抑制剂在调节心脏自主神经功能中的作用，特别关注心率变异性（HRV）作为自主神经平衡的生物标志物。这些药物通过增强糖尿、利钠和体重减轻来改善代谢状况，同时降低血压。重要的是，它们还能减轻交感神经系统的过度活动并促进副交感神经调节，这可能会降低不良心血管事件的风险。潜在机制不仅包括代谢作用，还包括抗炎和抗氧化作用，这些共同有助于改善内皮功能和血管健康。先进的HRV分析，包括传统的时域和频域方法以及非线性方法，已被证明在检测高危人群早期自主神经功能障碍方面具有重要价值。一些研究表明，SGLT-2抑制剂可能与HRV参数的改善有关，如增加的SDNN和RMSSD以及降低的LF/HF比值。然而，各研究结果并不一致，需要进一步研究来确定这些潜在影响的程度和机制。尽管这些发现很有前景，但进一步的标准化长期研究对于阐明SGLT-2抑制剂在自主神经功能障碍管理中的作用机制和最佳治疗策略至关重要。未来的研究还应探索将SGLT-2抑制剂与其他心脏代谢疗法联合使用的协同潜力，以改善患有和未患有T2DM的个体的心血管结局。
