Novelties in Medicinal Therapy of Uncontrolled Arterial Hypertension: SGLT2 Inhibitors and What Else?

Uncontrolled arterial hypertension (UAH remains one of the most challenging conditions in clinical practice, often exposing patients and clinicians to persistently elevated blood pressure (BP) levels despite optimal use of standard antihypertensive therapies. In this context, sodium-glucose co-transporter 2 inhibitors (SGLT2i), initially developed for the treatment of type 2 diabetes mellitus (T2DM), are emerging as promising agents in the management of BP regulation. Growing evidence demonstrates that these agents can effectively lower BP not only in patients with T2DM, but also in individuals with UAH, chronic kidney disease (CKD), and congestive heart failure (CHF), with effects that are sometimes independent of glycemic control. Unlike traditional anti-hypertensives, SGLT2 inhibitors exert multifactorial actions: they promote controlled osmotic diuresis, reduce plasma volume, improve endothelial function, and modulate sympathetic nervous system activity. This integrated approach facilitates more physiologic and sustainable BP control, opening new therapeutic avenues, particularly for patients with cardio-metabolic and renal comorbidities. This chapter explores the role of SGLT2i in the treatment of hypertension, with a focus on their mechanisms of action, recent clinical evidence, and future implications. The introduction of this drug class may represent a paradigm shift in the management of UAH, offering new opportunities for more effective and individualized therapeutic strategies.