In older adults with pulmonary hypertension, GLP-1 receptor agonist therapy was associated with reduced all-cause mortality compared with SGLT2 inhibitors (HR 0.940; 95% CI 0.885-0.997).
Cohort (n=26,848)
Yes
Does GLP-1 receptor agonist therapy reduce adverse cardiopulmonary outcomes and mortality compared to SGLT2 inhibitors in adults aged 70 years and older with pulmonary hypertension?
In older adults with pulmonary hypertension, GLP-1 receptor agonists may offer superior cardiopulmonary and mortality benefits compared to SGLT2 inhibitors.
Effect estimate: HR 0.940 (95% CI 0.885-0.997)
Abstract Rationale Pulmonary hypertension (pHTN) in older adults is often associated with high rates of cardiopulmonary complications. While glucagon-like peptide-1 receptor agonists (GLP1As) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) have demonstrated cardiovascular and pulmonary benefits, their comparative effects in patients with pHTN remain unclear. This study evaluated cardiopulmonary and clinical outcomes associated with GLP1A versus SGLT2I therapy in older adults with pHTN. Methods We conducted a retrospective, propensity score-matched cohort analysis using the TriNetX Research Network. Adults aged 70 years and older with a diagnosis of pHTN were identified and stratified by exposure to either GLP1As or SGLT2Is. After 1:1 propensity matching of 26,848 patients based on demographics, cardiometabolic comorbidities, and medication use, cardiopulmonary and clinical outcomes were compared between cohorts. Outcomes included all-cause mortality, emergency room visits, hospitalizations, intensive care unit (ICU) admissions, outpatient visits, heart failure, systolic heart failure, acute kidney injury (AKI), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels greater than 1,400 pg/mL, cardiomegaly, cardiac arrest, atrial fibrillation, ventricular tachycardia, cor pulmonale, respiratory failure, lung transplant, and diabetic ketoacidosis. Outcomes were analyzed using Kaplan-Meier survival curves with log-rank tests, and hazard ratios (HRs) with 95 percent confidence intervals (CIs) were estimated using Cox proportional hazards models. Results Compared with SGLT2I therapy, GLP1A therapy was associated with significantly lower hazards of multiple adverse cardiopulmonary outcomes. GLP1A users had reduced all-cause mortality (HR 0.940, 95% CI 0.885-0.997), hospital admissions (0.823 0.747-0.907), and ICU admissions (0.735 0.677-0.799). GLP1A therapy also lowered the risk of heart failure (0.632 0.579-0.689) and systolic heart failure (0.518 0.469-0.571). In addition, GLP1A use was associated with reduced risk of AKI (0.792 0.731-0.857) and NT-proBNP levels greater than 1400 pg/mL (0.698 0.619-0.786). Conclusion In older adults with pHTN, GLP1A therapy was associated with improved cardiopulmonary and renal outcomes, as well as lower mortality, compared with SGLT2I therapy. These findings highlight a potential therapeutic advantage of GLP1A-based strategies for cardiopulmonary and renal risk reduction in this high-risk population. This abstract is funded by: None
Chaaban et al. (2026) conducted a cohort in Pulmonary hypertension (n=26,848). GLP-1 Receptor Agonists vs. SGLT2 Inhibitors was evaluated on All-cause mortality (HR 0.940, 95% CI 0.885-0.997). In older adults with pulmonary hypertension, GLP-1 receptor agonist therapy was associated with reduced all-cause mortality compared with SGLT2 inhibitors (HR 0.940; 95% CI 0.885-0.997).