Sympathetic activity in patients with type 2 diabetes mellitus treated with empagliflozin or hydrochlorothiazide

Abstract

Reductions in sympathetic nervous system activity may contribute to beneficial effects of sodium glucose transporter (SGLT2) inhibition on cardiovascular outcomes. We hypothesized that SGLT2 inhibition with empagliflozin (Empa) lowers sympathetic activity compared with hydrochlorothiazide (HCT). The active comparator HCT was chosen to discern SGLT2-specific actions from non-specific responses to increased natriuresis. In this double-blind, randomized study, patients with type 2 diabetes mellitus on metformin monotherapy received either 25 mg/day Empa (n = 20) or 25 mg/day HCT Clin Auton Res (2022) 32:313–380 341 123(n = 21) for 6 weeks. Muscle sympathetic nerve activity (MSNA), blood pressure, cardiovascular, and metabolic biomarkers were assessed at baseline and at the end of treatment. Empa increased urinary glucose excretion (difference in change from baseline 47.4 mmol/l vs. HCT), reduced fasting plasma glucose, HbA1c, and body weight (all p\ 0.05). Office systolic blood pressure decreased with both treatments. MSNA, baroreflex heart rate control, and plasma catecholamines did not change significantly with either treatment. MSNA increased with higher body weight loss with both treatments, presumably related to intravasal volume depletion because of increased natriuresis. The relationship was shifted to lower MSNA with Empa as compared to HCT. In conclusion, neither Empa nor HCT treatment led to clinically relevant changes in sympathetic activity. Given the important role of the sympathetic nervous system in the progression of cardiovascular disease, mechanisms attenuating sympathetic activity in the face of increased sodium excretion deserve further attention.