Efficacy of SGLT2 Inhibitors in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Preclinical Studies

Abstract

BackgroundPulmonary arterial hypertension (PAH) is a progressive disease marked by vascular remodeling, elevated pulmonary pressures, and right ventricular failure. Current therapies are mainly vasodilatory, underscoring the need for treatments targeting additional pathways. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially used for diabetes, have demonstrated cardiovascular benefits. AimsThis systematic review and meta-analysis evaluated the effects of SGLT2 inhibitors in animal models of PAH, focusing on pulmonary hemodynamics and right ventricular function. MethodsPubMed, Embase, Web of Science, and Scopus were searched for preclinical studies reporting mean pulmonary artery pressure (mPAP), right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RV/LV+S), tricuspid annular plane systolic excursion (TAPSE), or pulmonary artery acceleration time (PAAT). Random-effects meta-analyses were performed using R. ResultsNine studies were included. SGLT2 inhibitors were significantly associated with lower mPAP (WMD -9.79 mmHg), RVSP (WMD -14.81 mmHg), and RV/LV+S (WMD -0.10). They were also associated with higher indices of right ventricular function, including TAPSE (WMD 0.53 mm) and PAAT (WMD 6.39 ms). ConclusionIn preclinical models of PAH, SGLT2 inhibitor treatment was associated with favorable hemodynamic and structural parameters. Further research is needed to clarify their translational potential and long-term safety.