This review synthesizes current evidence on the mechanistic rationale, preclinical findings, and clinical potential of repurposing SGLT2 inhibitors and MRAs for pulmonary arterial hypertension.
Do SGLT2 inhibitors and MRAs improve outcomes in patients with pulmonary arterial hypertension?
This review synthesizes current evidence on the mechanistic rationale and potential clinical benefits of repurposing SGLT2 inhibitors and MRAs for pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a progressive and life-threatening condition characterized by elevated pulmonary vascular resistance eventually causing right ventricular failure and premature death. Despite advances in targeted therapies, morbidity and mortality levels remain high, highlighting the need for additional treatment strategies that address the disease’s multifactorial pathophysiology. Attention has recently centred on two pharmacological groups with proven roles in other cardiovascular settings: sodium–glucose cotransporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs). SGLT2 inhibitors have demonstrated robust clinical benefits in heart failure (HF), type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), extending survival and reducing hospitalizations. Although their primary actions involve renal glucose and sodium handling, accumulating evidence suggests they may also exert favourable effects on the pulmonary vasculature, endothelial function, and right ventricular performance. In parallel, elevated aldosterone levels have been implicated in vascular remodelling, inflammation, and fibrosis in PAH, suggesting a potential therapeutic role for MRAs. However, the strength and clinical significance of these associations remain under investigation. The aim of this review is to synthesize and critically appraise the current evidence regarding the potential role of SGLT2 inhibitors and MRAs in the treatment of pulmonary arterial hypertension, exploring their mechanistic rationale, preclinical findings, and available clinical data to determine whether these agents may offer additional therapeutic benefit in PAH management.
Karkoulias et al. (Sun,) conducted a review in Pulmonary arterial hypertension. SGLT2 inhibitors and mineralocorticoid receptor antagonists was evaluated. This review synthesizes current evidence on the mechanistic rationale, preclinical findings, and clinical potential of repurposing SGLT2 inhibitors and MRAs for pulmonary arterial hypertension.