As GLP-1 use has expanded well beyond obesity and diabetes, clinicians are encountering a broader range of real-world symptoms — some anticipated, others less clearly defined.

One emerging issue is chronic cough: An observational analysis published in November in JAMA Otolaryngology–Head & Neck Surgery reported a higher incidence of persistent cough among patients taking GLP-1 receptor agonists than among those receiving other second-line therapies. This analysis suggests that chronic cough may occur in some patients taking GLP-1 receptor agonists even in the absence of documented gastroesophageal reflux disease (GERD), raising questions about how such symptoms should be interpreted in clinical practice.

For primary care providers (PCPs), the challenge is practical: how to evaluate a common symptom that may or may not be medication-related while preserving the substantial cardiometabolic benefits of continued therapy.

Interpreting an Emerging Signal 

Chronic cough has not traditionally been listed as a common adverse effect of GLP-1s. According to Jeff Stanley, MD, president of the Virta Medical Professional Corporation of Denver-based Virta Health, a provider-led, nutrition-first program that focuses on metabolic health and sustainable lifestyle changes, the recent findings should be viewed as hypothesis-generating rather than definitive.

“Primary care clinicians should view these findings as a reminder to expand their differential diagnosis when evaluating persistent cough but understand that this is currently a correlation,” he said. 

There was no significant increase in chronic cough in clinical trials for GLP-1 receptor agonists, and post-market surveillance may not adequately control for confounding factors, Stanley said. 

“Some patient populations may be at higher risk of cough while taking GLP-1s, including those with asthma, COPD [chronic obstructive pulmonary disease], sleep apnea, or prior GERD. It is possible that a higher prevalence of these conditions in post-marketing surveillance could be responsible for the slightly higher incidence of chronic cough that has been seen,” he said. 

These conditions should not be considered a contraindication for GLP-1 medications, “but PCPs may want to discuss the possible risk with patients and ask them to report back.”

Stephanie Walsh, MD, MS, co-founder of ProCare TeleHealth, said that although recent studies comparing GLP-1 therapy with other diabetes medications have reported a higher occurrence of chronic cough, this association is only beginning to be studied, and theories as to the mechanism behind it are few.

“There isn’t a consensus on why this cough is likely to develop,” Walsh said. “There is some thought that it may be due to gastric slowing and increasing GERD, although patients without GERD have developed the cough as well.”

Management When Cough Persists 

Walsh said that in most cases, conservative measures should be attempted before discontinuing therapy.

“Management of the cough is not yet established,” she said. “If a patient develops a cough, they should reach out to their physician, especially if they have any shortness of breath, difficulty breathing, or a fever. The physician may discuss options, including changing medications. 

Discontinuing the medication should generally be reserved for patients for whom other causes have been reasonably excluded and whose symptoms remain persistent or severe.

Stanley said that a trial of a different GLP-1 is also reasonable, especially because they have different side effect profiles, but he cautioned that this approach is not evidence-based. He said that other approaches could also be ruled out. 

“Nonstandard dosing schedules, such as every other week or beyond, are not currently recommended,” Stanley said. “Empiric reflux management is typically not recommended but could be considered if there is a strong indication to continue the medication — such as CAD [coronary artery disease], CKD [chronic kidney disease], or poorly controlled diabetes — and if dose reduction or switching to another GLP-1 medication is ineffective.”

Counseling Patients as GLP-1 Use Expands 

Stanley said that as the rate of prescribing GLP-1s continues to increase, clinicians should include chronic cough in shared decision-making conversations, without overstating the risk. 

“This does not appear to be common, and wasn’t seen in the clinical trials,” he said. “As with starting any new medication, it is important to encourage open communication from patients about any new side effects, particularly any red flag symptoms.”

He said that encouraging patients to report new or persistent symptoms, particularly those associated with breathing difficulty or systemic signs, supports timely evaluation while maintaining trust and adherence.

Stanley had no disclosures. Walsh is an advisor for Novo Nordisk A/S.