Investigating the Relationship Between Sodium–Glucose Cotransporter-2 (SGLT2) Inhibitors and Blood Pressure

Sodium-glucose cotransporter-2 (SGLT2) inhibitors were originally approved for use in type 2 diabetes, but in recent years, these medications were found to also have significant cardiovascular benefits in patients with heart failure with reduced and preserved ejection fraction and chronic kidney disease. Part of the cardiovascular benefits of SGLT2 inhibitors likely comes from their antihypertensive effect in addition to other unknown effects, but the mechanism by which these medications reduce blood pressure has not been identified yet. Multiple mechanisms have been proposed to describe SGLT2 inhibitors' antihypertensive effect, including their associated weight loss and diuretic effect. However, studies have shown that these indirect mechanisms alone do not account for the antihypertensive effect seen with this medication, with more recent studies identifying a new potential mechanism by which SGLT2 inhibitors may derive their direct antihypertensive and cardiovascular benefits. In animal models, SGLT2 receptors were identified in parts of the brain responsible for regulating the sympathetic nervous system and adjusting blood pressure. In these studies, SGLT2 inhibitors suppressed the neuronal activity in these brain regions, reducing the sympathetic nervous system activity and blood pressure of the animals. Further investigation is needed to identify whether there are SGLT2 receptors in the central nervous system of humans and whether SGLT2 inhibitors can suppress neuronal activity in these brain regions. This information could be significant in learning more about the susceptibility and severity of primary hypertension in certain patient populations, as well as identifying whether SGLT2 inhibitors can be considered as a primary antihypertensive agent.