Qubbaj, F.; Saeed, A.; Younis, O.; Al-Awamleh, N.; Al-Sharif, Z.; Shaban, Q.; Sulaiman, S.; Turk, A.

Background: Pulmonary 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. Aims: This systematic review and meta analysis evaluated the effects of SGLT2 inhibitors in animal models of PAH, focusing on pulmonary hemodynamics and right ventricular function. Methods: PubMed, 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. Results: Nine 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). Conclusion: In 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.