Emerging therapies: Potential roles of SGLT2 inhibitors in the management of pulmonary hypertension

ABSTRACT

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and may be associated with a variety of cardiovascular and respiratory diseases. Pulmonary hypertension due to left heart disease (PH-LHD) currently lacks targeted therapies, while Pulmonary arterial hypertension (PAH), despite approved treatments, carries considerable residual risk. Metabolic dysfunction has been linked to the pathogenesis and prognosis of PH through various studies, with emerging metabolic agents offering a potential avenue for improving patient outcomes. Sodium-glucose cotransporter 2 inhibitor (SGLT-2i), a novel hypoglycemic agent, could ameliorate metabolic dysfunction and exert cardioprotective effects. Recent small-scale studies suggest SGLT-2i treatment may improve pulmonary artery pressure in patients with PH-LHD, and the PAH animal model shows that SGLT-2i can reduce pulmonary vascular remodeling and prevent progression in PAH, suggesting potential benefits for patients with PH-LHD and perhaps PAH. This review aims to succinctly review PH's pathophysiology, and the connection between metabolic dysfunction and PH, and investigate the prospective mechanisms of action of SGLT-2i in PH-LHD and PAH management.