Abstract

Background: Obesity and type 2 diabetes mellitus (T2DM) are among the leading risk factors for mortality worldwide. Sodium-glucose co-transporter 2 Inhibitors (SGLT2i), such as empagliflozin, represent a last-generation drug class for T2DM treatment with cardiovascular benefits. This research project aims to investigate whether coexposure to aircraft noise affects the therapeutic efficacy of empagliflozin in an animal model of obesity.

Methods and Results: To induce obesity, we fed C57BL/6JRj mice a Western (high fat) Diet for 20 weeks. After 14 weeks, empagliflozin (10 mg/kg/d) treatment was applied via drinking water. To investigate the effects of aircraft noise, we additionally exposed the mice to aircraft noise for the last 4 days of the treatment period. Noise exposure alone interfered with glucose metabolism, increased blood pressure, impaired the endothelial function of the aorta, and increased vascular oxidative stress and inflammation. Six weeks of empagliflozin therapy improved blood glucose metabolism and vascular and oxidative parameters in high fat diet (HFD) animals. These therapeutic effects were attenuated or absent in animals exposed to additional aircraft noise.

Conclusions: SGLT2i, such as empagliflozin, are widely used in clinical practice beyond the treatment of T2DM. Our study demonstrates that additional exposure to aircraft noise can attenuate the protective effects of SGLT2 inhibitors in a murine obesity model. Considering personalized medicine progress, it is crucial to understand better the interaction of several risk factors, especially environmental stressors, in order to improve the therapeutic outcome of established medications and thus enable better protection of vulnerable groups.