Effects of luseogliflozin on sympathetic nerve activity:a dual assessment using iodine-123-metaiodobenzylguanidine and muscle sympathetic nerve activity
T Hirai, H Murai, C Nomura, H Sugimoto, Y Mukai, T Ikeda, Y Takeshita, K Sakata, S Usui, S Takata, T Takamura, M TakamuraAbstract
Introduction
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are reported to reduce the risk of cardiovascular disease, heart failure, and all-cause mortality in patients with type 2 diabetes. Reductions in sympathetic nervous activity (SNA) are thought to contribute to these cardiovascular benefits. Proposed mechanisms include reduced central sympathetic outflow via improved renal afferent nerve activity or direct effects on the central nervous system. However, the detailed mechanism remains unclear.
Methods
Twenty patients with type 2 diabetes (mean age, 60.5 ± 11.2 years; 13 men) were enrolled. We assessed cardiac and renal iodine-123-metaiodobenzylguanidine (I-123-MIBG) scintigraphy, muscle sympathetic nerve activity (MSNA) via microneurography, blood pressure, heart rate, and metabolic biomarkers at baseline and after 24 weeks of luseogliflozin (2.5 mg/day) administration. The early and delayed heart-to-mediastinum (H/M) and kidney-to-mediastinum (K/M) ratios, and washout rate were calculated.
Results
After 24 weeks, luseogliflozin treatment significantly decreased Hemoglobin A1c (7.2 ± 0.7 to 6.9 ± 0.5%) and MSNA (54.1 ± 12.7 to 42.8 ± 8.1 bursts/minute; both p < 0.05). From the I-123-MIBG, only the early renal K/M ratio decreased (2.48 ± 0.53 to 2.19 ± 0.64; p < 0.05). No significant changes were observed in blood pressure, heart rate, or other scintigraphic parameters.
Conclusions
24 weeks of luseogliflozin administration significantly decreased MSNA in patients with type 2 diabetes. Furthermore, I-123-MIBG scintigraphy revealed a reduction in the early uptake of MIBG in renal sympathetic nerve terminals. The effect of luseogliflozin might contribute to the improvement of the vicious interaction between the SNA and sympathetic outflow to the kidneys.