Glucagon-Like Peptide-1 Receptor Agonists and Chronic Cough

Importance Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become substantially more popular as a medication to treat obesity and type 2 diabetes (T2D). Despite their known association with gastroesophageal reflux disease and vagal nerve stimulation, the association between GLP-1RAs and chronic cough has not been previously studied. Objective To assess the clinical association between GLP-1RAs and chronic cough. Design, Setting, and Participants This large, multicenter cohort study used clinical records from a US-based collection of electronic medical record data from April 28, 2005, to April 15, 2025, from 70 health care organizations. Adults (≥18 years) with T2D and prescription of a GLP-1RA were identified. Additionally, groups with T2D and prescription of another second-line diabetes medication, including dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and sulfonylureas were created. After propensity score matching for various demographic and clinical characteristics, adjusted hazard ratios (aHRs) and 95% CIs were calculated using Cox regression analyses to estimate the risk of new chronic cough or gastroesophageal reflux disease diagnosis. Exposure GLP-1RAs or other second-line diabetes medication. Main Outcomes and Measures Chronic cough. Results Cohorts included 427 555 individuals (mean [SD] age, 55.8 [13.8] years; 251 928 female individuals [58.9%]) with T2D who were prescribed a GLP-1RA and 1 614 495 individuals (mean [SD] age, 63.7 [13.3] years; 712 946 female individuals [44.4%]) with T2D who were prescribed another second-line diabetes medication. After propensity score matching, individuals prescribed a GLP-1RA had significantly increased risk of new chronic cough compared with individuals prescribed any non–GLP-1RA second-line medication (aHR, 1.12; 95% CI, 1.08-1.16), DPP-4 inhibitor (aHR, 1.18; 95% CI, 1.11-1.26), or sulfonylurea (aHR, 1.32; 95% CI, 1.24-1.40) but not compared with SLGT2 inhibitors (aHR, 1.03; 95% CI, 0.98-1.09). After removing patients with a previous diagnosis of gastroesophageal reflux disease from analysis, patients prescribed GLP-1RAs had significantly increased risk of chronic cough compared with those prescribed any non–GLP-1RA (aHR, 1.29; 95% CI, 1.17-1.42), DPP4 inhibitor (aHR, 1.36; 95% CI, 1.17-1.58), SGLT2 inhibitor (aHR, 1.14; 95% CI, 1.02-1.28), or sulfonylurea (aHR, 1.25; 95% CI, 1.09-1.42). Conclusions and Relevance This cohort study suggests an association between GLP-1RA use and chronic cough. Further research is needed to confirm the existence, strength, and mechanisms of this association.