Although patients with pulmonary arterial hypertension (PAH) treated with glucagon-like peptide-1 (GLP-1) receptor agonists and SGLT2 inhibitors have comparable mortality rates, GLP-1 receptor agonists may significantly reduce right heart failure compared to sodium-glucose cotransporter-2 (SGLT2) inhibitors, according to an analysis of data from a large real-world platform.
PAH is a progressive, life-threatening disease that involves pulmonary vascular remodeling and can lead to right ventricular dysfunction and heart failure. GLP-1 receptor agonists and SGLT2 inhibitors benefit cardiovascular health in patients with type 2 diabetes and may affect pulmonary vascular function.
TriNetX Platform Data
The researchers used data from the TriNetX platform to investigate the medications’ comparative effects on all-cause mortality, respiratory failure, and right heart failure in patients with PAH. They examined data from adults diagnosed with group 1 PAH (precapillary pulmonary hypertension with increased pulmonary vascular resistance without other causes of precapillary pulmonary hypertension) from 2013 to 2021. Patients were followed for 3 years.
The study investigated 1,611 patients receiving GLP-1 receptor agonists without SGLT2 inhibitors and 2,124 patients taking SGLT2 inhibitors without GLP-1 receptor agonists. The researchers used propensity score matching to account for demographics, cardiovascular and respiratory conditions, endocrine disorders, cardiac and PAH medications, hemoglobin A1C, body mass index, and B-type natriuretic peptide (BNP) levels. After matching, each group included 1,121 participants, providing a balanced comparison of outcomes between GLP-1 receptor agonist and SGLT2 inhibitor use in patients with PAH.
At a mean follow-up of 713 days in patients taking GLP-1 receptor agonists and 557 days in those taking SGLT2 inhibitors, the investigators found no statistically significant difference in all-cause mortality between the groups (RR 0.906; 95% CI, 0.724-1.135; P=0.392), and no significant difference in respiratory failure risk (RR 0.929; 95% CI, 0.689-1.253; P=0.629).
However, the GLP-1 receptor agonist group showed a marked decrease in right heart failure compared to the SGLT2 inhibitors group (RR 0.464; 95% CI, 0.27-0.798; P=0.004), a 53.6% relative risk reduction. Also, the mean BNP level in the GLP-1 receptor agonist group (338) was much lower than in the SGLT2 inhibitor group (829), suggesting potential differences in cardiac stress between the two treatments.
This notably lower BNP level in the GLP-1 receptor agonist group suggests the medication’s potential benefits in cardiac function. The researchers highlight the necessity for randomized controlled trials to validate their observations and directly compare the efficacy and safety of GLP-1 receptor agonists and SGLT2 inhibitors in PAH management.
Reference
Alawad S, Al-Saeed N, Jarrar A, et el. Comparative Cardioprotective Effects of GLP-1 RA vs SGLT2i Inhibitors In Pulmonary Arterial Hypertension: Insights From a Large-Scale Real-World
Data Analysis. Presented at: CHEST 2025, October 19-22, 2025; Chicago.
