Abstract
Purpose of ReviewThe moderate glucose-lowering effect of sodium glucose co-transporter 2 (SGLT2) inhibitors is unlikely to explain SGLT2 inhibitor-mediated beneficial outcomes, and unravelling the underlying mechanisms is a high priority in the research community. Given the dominant pathophysiologic role of the sympathetic nervous system activation in conditions such as hypertension and perturbed glucose homeostasis, it is pertinent to postulate that SGLT2 inhibitors may exert their beneficial effects at least in part via sympathetic inhibition.Recent FindingsSGLT2 inhibitors have shown enormous potential to improve cardiovascular outcomes in patients with type 2 diabetes, and their therapeutic potential is currently being investigated in a range of associated comorbidities such as heart failure and chronic kidney disease. Indeed, recent experimental data in relevant animal models highlight a bidirectional interaction between sympathetic nervous system activation and SGLT2 expression, and this facilitates several of the features associated with SGLT2 inhibition observed in clinical trials including improved glucose metabolism, weight loss, increased diuresis, and lowering of blood pressure.SummaryCurrently available data highlight the various levels of interaction between the sympathetic nervous system and SGLT2 expression and explores the potential for SGLT2 inhibition as a therapeutic strategy in conditions commonly characterised by sympathetic activation.
Highlights
The sympathetic nervous system (SNS) is a crucial player in circulatory and metabolic control [1, 2]
It is obvious that these effects contribute substantially to blood pressure (BP) elevations, both acutely and in the long term, if occurring simultaneously and/or if sympathetic activation is sustained over a longer period of time
Our research team and others have demonstrated that sodium glucose co-transporter 2 (SGLT2) inhibition is associated with a reduction in SNS activity, inhibition of norepinephrine turnover in brown adipose tissue and a reduction of tyrosine hydroxylase
Summary
The sympathetic nervous system (SNS) is a crucial player in circulatory and metabolic control [1, 2]. Mahfoud et al reported that reduction of sympathetic activity by renal denervation in patients with resistant hypertension substantially improved glucose metabolism and insulin sensitivity, in addition to markedly reducing BP [15]. Beyond and independent of glycaemic control, clinical trials using SGLT2 inhibitors have demonstrated unprecedented cardio-renal benefits such as significantly reduced CV morbidity and mortality, lower rates of hospitalized heart failure, improved renal function and reduced progression of diabetic nephropathy [20, 28, 29, 30, 31] (Fig. 1). These interesting findings will later be discussed in detail
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