We welcome Drs. Foer and Cahill sharing their recent findings (1,2) on the association of glucagon-like peptide 1 receptor agonists with fewer respiratory disease exacerbations and providing their perspective on our study (3).
One of the main challenges researchers encounter when conducting comparative effectiveness studies of glucose-lowering agents is selecting the most appropriate comparator (4). An abundant number of factors influence the probability of receiving specific second-line agents, such as when the medication entered the market, cost-effectiveness, guideline recommendations, contraindications, and patient and prescriber preferences. Therefore, we decided to select dipeptidyl peptidase 4 inhibitors, rather than combining all second-line agents in one group, to minimize study participants' differences, including demographics, comorbidities, diabetes severity, and health care service utilization (as reflected in Table 1) (3).
Although the uncertainty interval in the asthma-only population included the null, the results should not be interpreted as a negative finding. We have stratified the analysis of our secondary outcome by chronic lower respiratory disease type, as suggested by Foer and Cahill, and while not significant for asthma, point estimates suggest a consistent effect on reduced exacerbations when comparing glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors (asthma-only population, relative ratio 0.77 [95% CI 0.58–1.01]; chronic obstructive respiratory disease–only population, relative ratio 0.52 [95% CI 0.37–0.74]).
We agree that our results, especially when considered jointly, provide ample justification for randomized trials to foster precision medicine and optimize treatment strategies for patients with diabetes.
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Duality of Interest. No potential conflicts of interest relevant to this article were reported.
