Chronic Cough Reported in Patients Using GLP-1 Drugs, Study Finds
USA: A new multicenter US cohort study has identified a potential link between the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs)—widely prescribed for type 2 diabetes and obesity—and an increased risk of chronic cough.
The findings, published in JAMA Otolaryngology–Head & Neck Surgery, suggest that patients taking these medications may be more likely to develop persistent cough symptoms compared with those using other second-line diabetes therapies. Researchers, however, caution that further investigation is necessary to better understand the strength of the association and the biological mechanisms behind it.
GLP-1RAs have gained significant popularity over the past decade due to their effectiveness in improving glycemic control, aiding weight loss, and providing cardiovascular and renal benefits. Despite their growing use, limited evidence exists regarding their potential respiratory adverse effects. Previous observations have noted associations between GLP-1RAs and gastroesophageal reflux disease (GERD), as well as vagal nerve stimulation—both of which could theoretically contribute to chronic cough. However, until now, this relationship had not been systematically evaluated.
The study, led by Tyler J. Gallagher from the Caruso Department of Otolaryngology–Head & Neck Surgery at the Keck School of Medicine, utilized a massive pool of electronic health records from 70 US health systems. The dataset included clinical information from April 2005 to April 2025, allowing the team to assemble one of the largest cohorts to date examining respiratory risks among GLP-1RA users.
A total of 427,555 adults with type 2 diabetes who were prescribed a GLP-1RA were compared with 1,614,495 patients who received different second-line medications such as DPP-4 inhibitors, SGLT2 inhibitors, and sulfonylureas. After applying propensity score matching to balance demographic and clinical factors, the researchers conducted Cox regression analyses to measure the risk of developing chronic cough.
To determine whether reflux-related cough contributed to these findings, the researchers conducted an additional analysis excluding individuals with known GERD.
Key findings:
- GLP-1RA users showed a modest but statistically significant increase in chronic cough compared with most other diabetes medication groups.
- The adjusted hazard ratio (aHR) for chronic cough was 1.12 when compared with all non–GLP-1RA medications.
- The risk increased further when compared specifically with DPP-4 inhibitors (aHR, 1.18) and sulfonylureas (aHR, 1.32).
- No significant difference in chronic cough risk was observed when comparing GLP-1RAs with SGLT2 inhibitors (aHR, 1.03).
- After excluding individuals with GERD, the association between GLP-1RA use and chronic cough remained and, in some cases, strengthened.
- In the GERD-free subgroup, GLP-1RA users had a 29% higher risk of chronic cough than users of non–GLP-1RA medications (aHR, 1.29).
- The elevated risk continued to be observed when compared separately with DPP-4 inhibitors, SGLT2 inhibitors, and sulfonylureas.
While the study does not establish causation, the authors note that these observations raise important questions for clinicians and patients using or considering GLP-1RAs. They emphasize the need for dedicated mechanistic studies to explore whether drug-induced changes in gastric motility, neural pathways, or airway sensitivity may be contributing factors.
"As GLP-1RAs continue to be prescribed at unprecedented rates, understanding their full safety profile—including potential respiratory effects—remains a critical area for future research," the authors concluded.
Reference:
Gallagher TJ, Razura DE, Li A, Kim I, Vukkadala N, Barbu AM. Glucagon-Like Peptide-1 Receptor Agonists and Chronic Cough. JAMA Otolaryngol Head Neck Surg. Published online November 26, 2025. doi:10.1001/jamaoto.2025.4181
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