A65-06 Glucagon-Like Peptide-1 Receptor Agonist Use in Patients With Pulmonary Arterial Hypertension

Abstract Rationale Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were developed to treat type 2 diabetes but have subsequently been found to promote weight loss and exert broadly beneficial cardiometabolic effects. Insulin resistance has been established as a key feature in pulmonary arterial hypertension (PAH) and is implicated in disease progression and right ventricular (RV) failure. These data suggest that GLP-1RAs may benefit patients with PAH, however their use and safety in PAH is not well understood. We sought to characterize GLP-1RA use among individuals with PAH. Methods We conducted a retrospective cohort study at our PAH referral center using de-identified electronic health record data with a validated method for identification of PAH cases. Among PAH cases, GLP-1RA users were matched to non-users by age, sex, and race at a maximum ratio of 10:1. We abstracted baseline characteristics closest to the date of GLP-1RA prescription or a pseudo-baseline date established for control patients corresponding to the time from diagnosis to GLP-1RA prescription of their matched GLP-1RA recipients. Controls with pseudo-baseline dates occurring after the date of death or in the future were excluded. Between group comparisons were conducted using Wilcoxon rank sum tests for continuous variables and chi-squared tests for categorical variables. Mortality was compared between groups using the log-rank test. Results We identified 887 subjects with PAH, of whom 41 (4.6%) received a GLP-1RA prescription after diagnosis. GLP-1RA users were effectively matched to 294 non-users by age (52 vs 52 years), sex (91.8% vs 92.7% female), and race (63.4% vs 72.0% white). Compared to non-users, GLP-1RA users had a higher BMI (38 vs 28, p 0.01), and LVEF (60% vs 55%, p = 0.13) with otherwise comparable echocardiographic, hemodynamic, and medication use characteristics. Hyperlipidemia, diabetes, and heart failure were more common in GLP-1RA users (all p 0.05). Full characteristics are displayed in Table 1. Over median follow up of 991 days for GLP-1RA users and 3,120 days for non-users, 6 and 67 deaths occurred, respectively (log-rank p = 0.56). Conclusion To our knowledge, this is the first description of GLP-1RA use in patients with PAH. We found that GLP1-RA users had greater metabolic disease burden than non-users. Future studies will require close attention to confounding from comorbidities and clinical status. Given recent expansion of GLP-1RA indications, we expect the prevalence within this population to increase. Clinical trials and prospective mechanistic studies are needed to evaluate the role of GLP-1RA therapy in the treatment of PAH. This abstract is funded by: None