Association of novel antihyperglycaemic drugs versus metformin with COPD exacerbations.

Background: 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 contribute to better control of COPD due to their anti-inflammatory effects, like those observed with metformin. We aimed to investigate the association of these novel antihyperglycaemic drugs versus metformin with fewer COPD exacerbations in patients with type 2 diabetes (T2DM) comorbid with COPD.

Methods: Using the national administrative database covering 99% of the medical facilities in Japan, we constructed three active comparators new-user cohorts comprising 36 317 patients with T2DM and COPD who initiated treatment with the novel antihyperglycaemic drugs and metformin between 2014 and 2022. Patients' backgrounds were balanced using overlap propensity score weighting. We calculated the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the initial occurrence of COPD exacerbation requiring systemic corticosteroids using a weighted Cox proportional hazards model.

Results: DPP-4 Is were associated with a higher incidence of exacerbations requiring systemic corticosteroids (22.4 versus 20.4 per 100 person-years; HR 1.16, 95% CI 1.07-1.25) compared with metformin. In contrast, the incidence of such exacerbations in the GLP-1 RAs (30.1 versus 24.4 per 100 person-years; HR 1.07, 95% CI 0.87-1.32) and SGLT-2 Is (20.7 versus 21.8 per 100 person-years; HR 1.00, 95% CI 0.94-1.06) groups were comparable with that in the metformin group.

Conclusions: While DPP-4 Is were associated with poorer control of COPD compared with metformin, GLP-1 RAs and SGLT-2 Is offered COPD control comparable with that of metformin.