Spotlight on GLP-1 receptor agonists and the lungs

Multiple recent studies looked into the possibility that glucagon-like peptide-1 (GLP-1) receptor agonists have beneficial effects on the lungs.

One study, published in the April 1 American Journal of Respiratory and Critical Care Medicine, analyzed adults with type 2 diabetes and asthma. It used an electronic database to compare new users of GLP-1 receptor agonists (n=448), with new users of sodium–glucose cotransporter-2 inhibitors (n=112), dipeptidyl peptidase-4 (DPP-4) inhibitors (n=435), sulfonylureas (n=2,253), or basal insulin (n=2,692). At six months, the patients on GLP-1 receptor agonists had significantly fewer asthma exacerbations than those on the other drug classes (incidence rate ratios, 2.98, 2.45, 1.83, and 2.58, respectively). They also had fewer health care encounters for asthma symptoms. The study results led the authors to conclude that GLP-1 receptor agonists “may represent a novel treatment for asthma associated with metabolic dysfunction,” and they called for prospective studies to validate their findings and understand the mechanisms.

Another study, published by Diabetes Care on April 19, used a claims database to look at adults with type 2 diabetes and chronic lower respiratory disease who began taking either a GLP-1 receptor agonist (n=4,150) or a DPP-4 inhibitor (n=12,540). During a year of follow-up, patients on GLP-1 receptor agonists had a significantly lower adjusted incidence of hospitalization for respiratory disease: 10.7 versus 20.3 per 1,000 person-years (adjusted hazard ratio, 0.52; 95% CI, 0.32 to 0.85). The same was true for the secondary outcome of exacerbations requiring an inpatient or outpatient visit (incidence rate ratio, 0.70; 95% CI, 0.57 to 0.87). The authors offered some “plausible mechanistic pathways” for the observed effects on lung disease and suggested that these benefits should be considered in the personalized selection of diabetes treatment regimens, including by guideline developers. They called for randomized clinical trials to confirm the findings.

Finally, a meta-analysis published by the Clinical Respiratory Journal on April 7 compiled seven randomized placebo-controlled trials of GLP-1 receptor agonists to assess rates of respiratory disorders. A total of 55,922 participants were included. Their incidence of these disorders was low, ranging from 0.02% for pulmonary fibrosis to 2.31% for pneumonia. However, the analysis found trends toward patients on GLP-1 receptor agonists having reduced rates of pneumonia, squamous-cell carcinoma of the lung, asthma, and chronic obstructive pulmonary disease and a higher rate of interstitial lung disease, although none of the differences were statistically significant. The authors concluded that the low rate of respiratory disorders led their analysis to be insufficiently powered but that this association should be studied further.