New research presented at this year's European Congress on Obesity in Istanbul, Turkey (12-15 May) shows the use of the new GLP-1 class of obesity drugs in people with asthma is associated with a 26% fall in the number of asthma exacerbations and a 14% drop in use of asthma inhaler reliever use. The study is by Simon Høj and Dr Kjell Erik Julius Håkansson Copenhagen University Hospital, Copenhagen Denmark and colleagues.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now widely used to treat overweight, obesity and type 2 diabetes (T2DM), with growing evidence of benefits that extend beyond blood sugar control.
In asthma, where overweight, obesity and metabolic dysfunction can lead to increased severity of symptoms and adverse events such as acute exacerbations, the authors suggest that GLP-1 RAs may improve asthma outcomes through weight loss, modulation of airway inflammation, and improvements in metabolic functions. Reductions in occurrence of asthma exacerbations are likely to reduce systemic corticosteroid exposure (a common treatment for acute asthma exacerbations orally or intravenously) and thus may reduce the risk of corticosteroid exposure-associated adverse events such as osteoporosis or new-onset T2DM. As such, as the clinical use of GLP-1 RAs expands, reliable estimates of their impact on asthma control are needed for individuals living with both asthma and overweight, obesity or T2DM.
The researchers conducted a nationwide self-controlled cohort study using linked Danish health registers. Adult individuals with a prior asthma diagnosis or ≥2 asthma inhaler prescriptions redeemed within 12 months) were included on the date of their first GLP-1 RA dispensing (index date). Eligible individuals had continuous registration data for at least 12 months before and after the index date.
Individuals with COPD or patients with severe asthma treated with new and relatively expensive biologic drugs within 12 months before or after the index date were excluded. Overweight or obesity was defined using ICD-10 codes for those conditions. Those who had no evidence of T2DM - with no diagnosis recorded or no evidence of other first line diabetes drugs prescribed - were also placed in the with obesity/overweight group. Those with a T2DM diagnosis or prescriptions recorded for first line diabetes drugs such as metformin were placed in the T2DM group.
The primary outcome was exacerbations, defined as an inpatient asthma hospital contact(s) and/or systemic oral or intravenous corticosteroid course(s). Secondary outcomes were the use of rescue medication (inhaled short-acting β2-agonists), inhaled corticosteroid exposure, and chest infection events defined as redemption of antibiotics commonly used for lower airway infections
The cohort comprised 27,523 individuals (mean age 54 years, 66% female) with asthma and comorbid overweight or obesity (49%) or T2DM (61%) and 26% recorded as having both conditions. Around 50% of the GLP-1 prescriptions were liraglutide, 48% semaglutide, and 2% others (exenatide, dulaglutide, lixisenatide).
Compared with the year before GLP-1 RA treatment, GLP-1 RA treatment was associated with a 26% lower exacerbation rate overall; and 28% lower in men compared with 23% lower in women. When stratified according to GLP1 RA treatment indication, the analysis showed individuals with asthma and comorbid overweight or obesity and individuals with asthma and comorbid T2DM had similar effect estimates – a 22% reduction in those with overweight or obesity and a 26% reduction in those with T2D.
Reliever medication use fell by 14% overall, suggesting fewer symptoms despite daily inhaled corticosteroid exposure also decreasing by 23% (inhaled corticosteroids are used to prevent exacerbations and treat symptoms in asthma). Furthermore, pneumonia events were reduced by 10%. People also living with allergic rhinitis saw similar decreases (23%) in exacerbations to those living without allergic rhinitis (28%). The authors are also working on updated analyses to show differences between men and women for these specific outcomes.
The authors conclude: "In this nationwide cohort of over 27,000 individuals with asthma and also overweight, obesity or type 2 diabetes, use of GLP-1 drugs was associated with significant reductions in exacerbation burden as well as reliever use, exposure to inhaled corticosteroids and pneumonia events, irrespective of whether the drugs were being used to treat obesity or type 2 diabetes."
The authors explain that their study did not have access to clinical records (just if people had used GLP-1 and hospital admissions), so data on BMI and weight loss for participants were not available.
But Dr Håkansson says: "There's a high chance that the weight loss is a major contributor to these results. A common symptom in both asthma and obesity is shortness of breath, and the presence of excess fatty tissue creates a pro-inflammatory state in the body in general. There's also evidence from other studies suggesting that the inflammation caused by excess adipose tissue is distinct from the 'classic' asthma inflammation which often is driven by allergies or cells called eosinophils."
And he adds: "As the use of GLP-1 therapies increase, researchers are finding an increasing number of effects outside of weight loss."
