They’ve been hailed as miracle drugs, helping millions shed stubborn pounds and cutting the risk of heart attack and stroke by around 20 per cent.
But as the use of GLP-1 weight-loss jabs has soared, doctors say they are also seeing more patients in A&E with severe vomiting, dehydration and complications linked to gallbladder disease and acute pancreatitis.
Now, new research suggests millions taking the injections could also face a greater risk of developing a chronic cough.
A chronic cough is one that lasts longer than eight weeks. It can be debilitating and may cause sharp chest pain as the muscles of the chest wall and diaphragm repeatedly contract.
The condition is thought to affect between eight and 10 per cent of adults and can be triggered by asthma and smoking, as well as certain medications.
Researchers at the Keck School of Medicine at the University of Southern California found that people taking GLP-1 drugs were 12 to 25 per cent more likely to develop a persistent cough than those using other second-line diabetes treatments.
The study analysed health data from more than two million people with type 2 diabetes.
Of these, 427,555 patients were taking GLP-1 receptor agonists. They were compared with around 1.6million people using other second-line diabetes medications.
New research suggests millions taking the injections could also face a greater risk of developing a chronic cough
Chronic cough has not traditionally been listed as a common side effect of GLP-1 drugs.
But the analysis revealed a small yet noticeable increase in cough diagnoses among patients using the medications.
The association was even stronger in patients who had never been diagnosed with gastroesophageal reflux disease (GERD), a condition in which stomach acid flows back into the oesophagus and is a known cause of chronic cough.
The finding, published in the journal JAMA Otolaryngology-Head & Neck Surgery, surprised researchers, who had initially suspected reflux disease might explain the link.
To test this theory, the researchers repeated their analysis after excluding anyone who had previously been diagnosed with GERD.
The unexpected result was that the association between GLP-1 drugs and chronic cough not only remained but appeared even stronger.
The researchers suggested the drugs might trigger coughing through a different form of reflux known as laryngopharyngeal reflux (LPR).
This occurs when stomach contents, such as acid and digestive enzymes, travel up into the throat without causing the typical burning sensation associated with heartburn.
Scientists believe this could be linked to the way GLP-1 drugs slow stomach emptying – a key mechanism that helps people feel fuller for longer and lose weight.
Slower gastric emptying can sometimes allow stomach contents to move further up the digestive tract, irritating sensitive tissues in the throat and potentially triggering the cough reflex.
Another possible explanation involves the vagus nerve, which plays a key role in controlling coughing.
Because GLP-1 receptors are also found in tissues in the throat and lungs, researchers suggested the drugs could potentially stimulate nerve pathways involved in the cough reflex.
However, the scientists stressed that the findings do not prove the medications directly cause chronic cough.
According to Jeff Stanley, MD, president of the Virta Medical Professional Corporation of Denver-based Virta Health, the results should be viewed as an early signal rather than definitive evidence.
‘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.
Stanley added that clinical trials of GLP-1 receptor agonists did not show a significant increase in chronic cough.
He said post-marketing data may also be influenced by other factors.
‘Some patient populations may be at higher risk of cough while taking GLP-1s, including those with asthma, COPD, sleep apnoea, or prior GERD,’ he said.
‘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 added that these conditions should not be considered a reason to avoid the medications but said doctors may wish to discuss the possibility with patients.
Stephanie Walsh, co-founder of ProCare TeleHealth, said that while several studies have observed a link between GLP-1 therapy and chronic cough, researchers still do not fully understand why it might occur.
‘There isn’t a consensus on why this cough is likely to develop,’ she said.
‘There is some thought that it may be due to gastric slowing and increasing reflux, although patients without GERD have developed the cough as well.’
Walsh said most cases should be managed conservatively rather than immediately stopping the medication.
‘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 shortness of breath, difficulty breathing or a fever.’
Doctors may consider changing medications or investigating other possible causes, she added.
Discontinuing GLP-1 therapy is generally recommended only when other explanations have been ruled out and symptoms remain persistent or severe.
Stanley said trying a different GLP-1 drug may also be reasonable in some cases, as individual medications can have different side-effect profiles.
However, he cautioned that there is currently limited evidence to guide this approach.
He also warned that nonstandard dosing schedules, such as taking the medication every other week, are not recommended.
‘Empiric reflux management is typically not recommended,’ he said, although it could be considered if there is a strong reason to continue the medication, such as coronary artery disease, chronic kidney disease or poorly controlled diabetes.
As prescriptions for GLP-1 medications continue to rise, Stanley said doctors should discuss possible side effects with patients without overstating the risk.
‘This does not appear to be common, and it 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.’
Encouraging patients to report persistent or unusual symptoms, he added, allows doctors to investigate early while maintaining trust and adherence to treatment.
