Asthma, COPD Attacks Down With GLP-1 Drugs in the Picture

Growing evidence linked GLP-1 drugs to a reduced risk of exacerbations of two types of chronic airways disease: asthma and chronic obstructive pulmonary disease (COPD).

Based on real-world records from the U.K., affected patients who went on any GLP-1 receptor agonist for a comorbid condition had a 14% lower risk of asthma or COPD exacerbation (defined as a short course of oral steroids, emergency department visit, hospitalization, or death) compared with new users of sulfonylureas.

The association varied by the specific GLP-1 agent: semaglutide (Ozempic, Wegovy) was tied to a significant 30% reduction in exacerbations, exenatide (Byetta, Bydureon) a 23% reduction, and dulaglutide (Trulicity) a 12% reduction, reported Chloe Bloom, MBChB, MSc, PhD, of Imperial College London.

The observational study was presented at the European Respiratory Society (ERS) Congress, held this year in Barcelona, Spain.

“The findings from this study are encouraging, but they should not change treatment decisions on their own. People with asthma or COPD should not start GLP-1 receptor agonists specifically for their lung condition outside current prescribing guidance. While the findings suggest that some people taking GLP-1 receptor agonists may experience fewer respiratory attacks, this needs confirmation in clinical trials,” Bloom said in a press release.

Of note, GLP-1 agonist results differed according to a person’s respiratory phenotype in the study. Semaglutide, for one, was associated with a 38% reduction in exacerbations in asthma and 21% in COPD.

Metabolic phenotype, on the other hand, seemed to have no bearing. Semaglutide’s effects did not appear to be modified by baseline body mass index, HbA1c, insulin resistance, change in weight during treatment, or change in glycemic control during treatment. “Metabolic factors did not appear to significantly influence effects, supporting the possibility of direct pulmonary mechanisms,” Bloom suggested.

Overweight and obesity are known risk factors for chronic respiratory diseases and their exacerbations. The study by Bloom and colleagues extends the interest in the potential lung-protective effects of GLP-1 receptor agonists, a wildly popular drug class officially used for treatment of type 2 diabetes and obesity, as well as cardiovascular protection.

“This is one of the largest real-world studies to investigate GLP-1 receptor agonists and airways disease, and one of the first to examine whether effects differ between individual GLP-1 receptor agonists,” Alexander Mathioudakis, MD, PhD, of the University of Manchester in England, said in a statement.

Given the study’s observational nature and inability to show causation, several experts stressed the need for randomized trials on GLP-1 drugs and asthma or COPD.

“We need clinical trials that include respiratory outcomes, such as asthma attacks, COPD exacerbations, lung function, symptoms, and quality of life, to determine whether metabolic treatments could become part of a broader, more personalized approach to managing airways disease,” according to Mathioudakis.

In comments posted to the Science Media Centre website, Marie Spreckley, PhD, of the University of Cambridge in England, agreed: “It is too early to state that semaglutide reduces or prevents asthma attacks. People should not seek semaglutide specifically for asthma or change their existing asthma treatment because of these findings. Randomized trials are needed to determine whether semaglutide provides a genuine respiratory benefit.”

Bloom’s team performed the study using electronic health records from the U.K.

From over 1.1 million adults identified as having asthma or COPD, the investigators identified a new-user cohort split between new users of GLP-1 drugs (n=8,266) and sulfonylureas (n=20,273) for other conditions, such as diabetes. Weighted propensity scoring was employed to compare these two groups.

Results suggested that asthma and COPD exacerbations did not appear to be modified by age, smoking, and eosinophil count.

Additionally, there was no change in exacerbations when patients started taking liraglutide (Victoza, Saxenda) or lixisenatide (Adlyxin), unlike the aforementioned GLP-1 drugs.

“It is not clear if the beneficial finding for semaglutide and lack of beneficial findings for other similar drugs is a true indicator of a specific effect, or a statistical anomaly — a chance finding. It may simply be that we can make a stronger claim about semaglutide because we have more data on this drug,” commented Stephen Burgess, PhD, also of the University of Cambridge, writing on the Science Media Centre.

“Clinical trials estimate average effects across the population, which are representative of overall trends rather than predictions of benefit for each individual,” Burgess added. “Still, GLP-1 receptor agonists can lead to life-changing reductions in body weight, and so it is both logical and heartening that we see evidence for beneficial effects on conditions that are hypothesized to be consequences of obesity.”