Researchers from the University of Aberdeen and the Observational and Pragmatic Research Institute have demonstrated that GLP-1 receptor agonists, commonly prescribed for diabetes and weight loss, significantly improve asthma control in obese patients. The study, published in Advances in Therapy, analyzed medical records from over 60,000 patients and found compelling evidence for respiratory benefits that extend beyond the drugs' established metabolic effects.
Study Design and Patient Population
The research team examined data from the Optimum Patient Care Research Database, comparing 10,111 patients taking GLP-1 drugs with 50,555 matched controls. All participants were over 18 years old, had a body mass index greater than 30 kg/m², and had received asthma consultations within 12 months before GLP-1 prescription initiation. Each GLP-1 user was matched 5:1 with controls who had similar characteristics but had never received GLP-1 medications.
The study followed participants for an average of three years, tracking baseline risk domain asthma control (RDAC) and overall asthma control (OAC) scores. Measures of asthma control included prescriptions for oral corticosteroids, recorded exacerbations, and hospital admissions.
Significant Improvements Despite Modest Weight Loss
Despite the GLP-1 group having higher average BMI and worse baseline asthma control, participants showed "significant" improvements in asthma scores after one year of treatment. Notably, these benefits occurred with relatively modest weight loss of approximately 0.9 kg over the study period.
"We found compelling evidence that GLP-1s, as well as increasing weight loss, also improved asthma symptoms," said Professor David Price, chair of primary care respiratory medicine at the University of Aberdeen. "In addition, it is important to note that the benefits to asthma symptoms occurred despite fairly modest weight loss of around 0.9 kg over the course of the year."
Anti-Inflammatory Mechanisms Beyond Weight Reduction
The research suggests that GLP-1 drugs' benefits for asthma control may stem from direct anti-inflammatory effects rather than weight loss alone. GLP-1 receptor agonists reduce inflammatory cells and factors through multiple signaling pathways, increase expression of anti-inflammatory factors, and alleviate inflammatory responses.
Dr. Jimmy Johannes, a pulmonologist at MemorialCare Long Beach Medical Center, explained the potential mechanism: "GLP-1 receptor agonists may be able to directly reduce the inflammation and airway hyperresponsiveness that contribute to asthma." He noted that GLP-1 receptors are present in the lungs, supporting the possibility of direct respiratory effects.
The study authors observed that "obese asthmatics are unique in that they are often steroid-resistant, and it is possible that mechanistic differences in obese asthmatics and weight loss with GLP1 may have pleomorphic effects on inflammation beyond just weight loss."
Addressing Treatment Challenges in Obese Asthma Patients
The findings are particularly relevant given the treatment challenges faced by obese asthma patients. Professor Alan Kaplan, chairperson of the Family Physician Airways Group of Canada, highlighted the "difficulty in achieving weight loss in patients with obesity and asthma, which is often made worse by the need for oral steroids to treat flare ups of asthma."
Additionally, obese patients demonstrate reduced response to standard asthma medications. "Obese patients have some degree of resistance to ICS use, leading to more difficulty getting control and [a] need to consider different agents," Kaplan explained.
Clinical Implications and Future Directions
The research positions GLP-1 drugs as a promising alternative to existing steroid treatments for obese asthma patients. "Weight loss improves asthma management. It improves control, reduces exacerbations and often allows reduction in asthma medications," Kaplan concluded. "The data in this study show similarly that use of a GLP-1RA can also have efficacy."
However, some experts urge caution in interpreting the results. Dr. Thomas Kilkenny from Northwell's Staten Island University Hospital suggested that "the improvements could be related to weight loss" rather than direct drug effects, noting that "weight loss alone improves asthma control" based on previous studies.
The researchers acknowledge that further investigation is needed to establish whether GLP-1 medications could be formally indicated for respiratory conditions. The study's lung function measurements were limited due to missing data during the COVID-19 pandemic, highlighting the need for additional research to fully characterize these drugs' respiratory effects.
These findings contribute to the expanding understanding of GLP-1 drugs' therapeutic potential beyond their established roles in diabetes and weight management, joining recent evidence of benefits for cancer risk reduction and dementia prevention.
