0
0
February 25, 2026
As glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide and tirzepatide continue to revolutionize the treatment of obesity, type 2 diabetes, and cardiovascular disease, their “real-world” side-effect profile is expanding. While nausea and gastrointestinal upset remain the most cited concerns, a new clinical signal has emerged that is catching the attention of primary care physicians: a persistent, chronic cough.
A recent observational analysis published in JAMA Otolaryngology–Head & Neck Surgery has sparked a medical dialogue after reporting a higher incidence of persistent cough among patients taking GLP-1s compared to those on other second-line therapies. Crucially, the study suggests this cough may occur even in patients without a history of gastroesophageal reflux disease (GERD), challenging the assumption that the symptom is merely a byproduct of delayed gastric emptying.
For the millions of Americans currently prescribed these “blockbuster” medications, the findings raise a practical dilemma: How should patients and providers manage a nagging cough without sacrificing the profound cardiometabolic benefits of the therapy?
Interpreting the “Cough Signal”
Chronic cough—defined as a cough lasting eight weeks or longer—was not a prominent feature in the large-scale clinical trials that led to the FDA approval of major GLP-1 medications. However, as the drugs move from controlled trial environments to millions of diverse users, rare or nuanced side effects often surface.
“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,” says Jeff Stanley, MD, president of Virta Medical Professional Corporation. Dr. Stanley notes that because this signal did not appear significantly in initial trials, the recent data should be viewed as “hypothesis-generating” rather than a definitive causal link.
The discrepancy between clinical trials and real-world data often comes down to the patient population. Post-market surveillance includes individuals with complex medical histories that trial participants might not have.
“Some patient populations may be at higher risk of cough while taking GLP-1s, including those with asthma, COPD, sleep apnea, or prior GERD,” Dr. Stanley explains. “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.”
The Mechanism Mystery: Is it Reflux or Something Else?
One of the most common side effects of GLP-1s is gastroparesis, or slowed stomach emptying. In theory, this can lead to “silent reflux,” where stomach acid or enzymes irritate the upper airway, triggering a cough. However, the JAMA analysis indicated that even patients without documented GERD were experiencing the symptom.
Stephanie Walsh, MD, MS, co-founder of ProCare TeleHealth, emphasizes that the medical community is still in the early stages of understanding this connection. “There isn’t a consensus on why this cough is likely to develop,” Dr. Walsh says. “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.”
Researchers are currently investigating whether GLP-1 receptors in the lungs or the central nervous system play a role in the cough reflex, though these theories remain speculative.
Clinical Management: When to Stay the Course
For patients experiencing a new cough while on a GLP-1, the advice from experts is clear: Do not stop the medication abruptly without consulting your doctor. Given the significant protection these drugs offer against heart disease and kidney failure, the goal is often “symptom management” rather than “treatment discontinuation.”
Steps for Evaluation
-
Rule out Infection: Clinicians must first ensure the cough isn’t related to a respiratory infection, such as bronchitis or COVID-19.
-
Screen for Red Flags: Dr. Walsh advises that patients should reach out immediately if a cough is accompanied by shortness of breath, difficulty breathing, or a fever.
-
Conservative Measures: Before switching medications, doctors may suggest lifestyle adjustments to mitigate potential reflux, such as eating smaller meals or avoiding food close to bedtime.
-
The “Switch” Strategy: If the cough persists, Dr. Stanley suggests that a trial of a different GLP-1 medication may be reasonable, as different molecules in the class have slightly different side-effect profiles. However, he cautions that this approach is not yet backed by robust clinical evidence.
“Discontinuing the medication should generally be reserved for patients for whom other causes have been reasonably excluded and whose symptoms remain persistent or severe,” says Dr. Walsh.
The Path Forward: Shared Decision-Making
As GLP-1 use expands to treat conditions ranging from sleep apnea to fatty liver disease, the conversation between patient and provider must become more nuanced.
Dr. Stanley recommends that clinicians include the possibility of a chronic cough in shared decision-making conversations, though he warns against overstating the risk. “This does not appear to be common,” he says. The priority remains maintaining open lines of communication so that “red flag” symptoms can be caught early without undermining the patient’s trust in their treatment plan.
For the patient, the takeaway is one of vigilance rather than alarm. If you find yourself clearing your throat or coughing more frequently after starting a GLP-1, keep a “symptom diary” to share with your primary care provider. This data can help determine if the cough is a minor, manageable side effect or a sign that a treatment adjustment is necessary.
References
Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.
