Association of novel antihyperglycemic drugs versus metformin with decrease in asthma exacerbations

Background Similar to metformin, dipeptidyl peptidase-4 inhibitors (DPP-4 Is), glucagon-like peptidase 1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2 Is) may improve control of asthma owing to their multiple potential mechanisms, including differential improvements in glycemic control, direct anti-inflammatory effects, and systemic changes in metabolism. Objective To investigate whether these novel antihyperglycemic drugs were associated with fewer asthma exacerbations compared with metformin in patients with asthma comorbid with type 2 diabetes. Methods Using a Japanese national administrative database, we constructed three active comparators—new user cohorts of 137,173 patients with a history of asthma starting the novel antihyperglycemic drugs and metformin between 2014 and 2022. Patient characteristics were balanced using overlap propensity score weighting. The primary outcome was the first exacerbation requiring systemic corticosteroids, and the secondary outcomes included the number of exacerbations requiring systemic corticosteroids. Results DPP-4 Is and GLP-1 RAs were associated with a higher incidence of exacerbations requiring systemic corticosteroids compared with metformin (DPP-4 Is: 18.2 vs. 17.4 per 100 person-years; hazard ratio 1.09, 1.05 to 1.14; GLP-1 RAs: 24.9 vs. 19.0 per 100 person-years; 1.14, 1.01 to 1.28). In contrast, the incidence of exacerbations requiring systemic corticosteroids was similar between the SGLT-2 Is and metformin groups (17.3 vs. 18.1 per 100 person-years; hazard ratio 1.00, 0.97 to 1.03). While DPP-4 Is and GLP-1 RAs were associated with more exacerbations requiring systemic corticosteroids, SGLT-2 Is were associated with slightly fewer exacerbations requiring systemic corticosteroids (53.7 vs. 56.6 per 100 person-years; rate ratio 0.95, 0.91 to 0.99). Conclusions While DPP-4 Is and GLP-1 RAs were associated with poorer control of asthma compared with metformin, SGLT-2 Is offered asthma control comparable to that of metformin.