Adjunctive GLP-1 Receptor Agonist Therapy Lowers Incident Pulmonary Hypertension and All-cause Mortality in Obese Patients with Obstructive Sleep Apnea Treated with PAP

ABSTRACT IMPORTANCE Obese subjects with obstructive sleep apnea (OSA) are at risk of pulmonary hypertension (PH) and mortality. Positive airway pressure (PAP) treatment lowers pulmonary artery pressures and mortality risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduces body weight and cardiovascular risk, but their effectiveness in OSA remains unexplored. OBJECTIVE To assess whether GLP-1 RAs is associated with lower incident PH and all-cause mortality at 1 and 3 years in obese patients with OSA treated with PAP. DESIGN Retrospective cohort study. SETTING US Collaborative TriNetX Global Database analysis performed on January 5, 2026 encompassing data from 56 centers during December 1, 2017 and December 25, 2025. PARTICIPANTS Obese patients diagnosed with OSA and treated with PAP (n=288,587). EXPOSURE Propensity score-matched comparisons of PAP vs PAP+semaglutide, PAP vs PAP+tirzepatide, PAP+semaglutide vs PAP+tirzepatide. MAIN OUTCOMES AND MEASURES Incident PH and all-cause mortality at 1 and 3 years. Risk ratios (RRs) with 95% CIs were estimated using the delta method; number needed to treat (NNT) was calculated from the absolute risk difference. RESULTS Compared with PAP, PAP+semaglutide was associated with lower incident PH at 1 year (RR:0.45; 95% CI:0.44–0.56, NNT=38) and at 3years (RR:0.50; 95% CI:0.45–0.54, NNT=23), and lower mortality at 1 year (RR:0.35; 95% CI:0.33–0.37, NNT=12) and 3 years (RR:0.37; 95% CI:0.35–0.39, NNT=8); PAP+tirzepatide was associated with lower incident PH at 1 year (RR:0.27; 95% CI:0.22–0.34, NNT=28) and 3 years (RR:0.22; 95% CI:0.18–0.27, NNT=15) and lower mortality at 1 year (RR:0.14; 95% CI:0.12–0.17, NNT=9) and 3 years (RR:0.12; 95% CI:0.10–0.14, NNT=6). Compared to PAP+semaglutide, PAP+tirzepatide showed lower incident PH at 1 year (RR:0.51; 95% CI:0.40–0.65, NNT=77) and 3 years (RR:0.42; 95% CI:0.34–0.51, NNT=39) and lower all-cause mortality at 1 year (RR:0.41; 95% CI:0.34–0.49, NNT=40) and 3 years (RR:0.33; 95% CI:0.28–0.39, NNT=22); all p-values