GLP-1 Receptor Agonists and Reductions of Disease Burden in Individuals with Asthma and Either Overweight, Obesity or Type 2 Diabetes: A Nationwide Self-Controlled Study
Abstract
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now widely used in overweight, obesity and type 2 diabetes (T2DM), with growing evidence of benefits that extend beyond glycemic control. In asthma, where overweight, obesity and metabolic dysfunction are strong disease modifiers, GLP-1 RAs may improve asthma outcomes through weight loss, modulation of airway inflammation, and improvements in metabolic functions. Even modest reductions in occurrence of asthma exacerbations are likely to reduce both systemic corticosteroid exposure and healthcare utilization. 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. Methods: We conducted a nationwide self-controlled cohort study using linked Danish health registers. Adult individuals with a prior asthma diagnosis ((ICD-10 J45/J46) or ≥2 respiratory prescriptions redeemed (ATC R03*) 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 treated with asthma biologics within ±12 months of the index date were excluded. Overweight or obesity was defined using ICD-10 codes (DE66*). The primary outcome was exacerbations, defined as an inpatient asthma contacts and/or new systemic corticosteroid courses with new events separated by ≥7 days. Secondary outcomes were the use of rescue medication (inhaled short-acting β2-agonists), inhaled corticosteroid (ICS) exposure, and pneumonia events. Results: The cohort comprised 27,523 individuals (mean age 54 (SD 6), 66% female) with asthma and comorbid overweight or obesity (49%) or T2DM (61%). Compared with the pre-exposure period, GLP-1 RA initiation was associated with a 26% lower exacerbation rate (IRR 0.74, 95% CI 0.69–0.80; p<0.001). When stratified according to GLP1 RA treatment indication, individuals with asthma and comorbid overweight or obesity and individuals with asthma and comorbid T2DM had similar effect estimates (overweight or obesity: IRR 0.78, 95% CI 0.70–0.87; p<0.001; T2DM: IRR 0.74, 95% CI 0.68–0.81; p<0.001). Secondary outcomes were directionally consistent: reliever medication use (IRR 0.86, 95% CI 0.78–0.94; p=0.002), pneumonia events (IRR 0.90, 95% CI 0.87–0.92; p=0.005), and ICS exposure (budesonide mcg equivalent exposure) (IRR 0.77, 95% CI 0.64–0.92; p=0.007). In sensitivity analyses, exacerbation effect estimates were consistent across sex (female: IRR 0.77, 95% CI 0.71–0.84; p<0.001; male: IRR 0.72, 95% CI 0.63–0.82; p<0.001) and comorbid allergic rhinitis (no rhinitis: IRR 0.77, 95% CI 0.71–0.83; p<0.001; rhinitis: IRR 0.72, 95% CI 0.61–0.85; p<0.001). Conclusions: In this nationwide cohort of over 27,000 individuals with asthma and comorbid overweight, obesity or T2DM, GLP1 RA initiation was associated with significant reductions in exacerbation burden as well as reliever use, exposure to inhaled corticosteroids and pneumonia events, irrespective of GLP1 RA treatment indication. Conflicts of Interest & Funding: This investigator-initiated study was funded by an unrestricted research grant from Novo Nordisk.
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