Incretin-based Drugs and the Prevention of Chronic Obstructive Pulmonary Disease Exacerbations Among Patients with Type 2 Diabetes

Background: There is some biological evidence suggesting that incretin-based drugs used for the treatment of type 2 diabetes may have beneficial effects in the treatment of chronic obstructive pulmonary disease (COPD) and reduce the risk of exacerbations. To date, however, real-world evidence for this potentially beneficial effect is limited.

Objectives: The objective of this study was to determine whether the use of incretin-based drugs is associated with a decreased risk of COPD exacerbations among patients with type 2 diabetes.

Methods: Using the United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics database, we assembled two separate active comparator new-user cohorts of patients with COPD who developed type 2 diabetes (2007-2019). The first cohort included 1252 initiators of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and 14,259 initiators of sulfonylureas, while the second cohort included 8731 initiators of dipeptidyl peptidase 4 (DPP-4) inhibitors and 18,204 initiators of sulfonylureas. Cox proportional hazards models with propensity score fine stratification weighting were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of severe COPD exacerbation (defined as hospital admission for COPD), separately for GLP-1 RAs and DPP-4 inhibitors. We also assessed whether these drugs were associated with a decreased risk of moderate exacerbations (defined as a co-prescription of an oral corticosteroid and an antibiotic along with an outpatient diagnosis of acute COPD exacerbation).

Results: Compared with sulfonylureas, GLP-1 RAs were associated with a 30% decreased risk of severe exacerbation (3.5 vs 5.0 per 100 person-years, respectively; HR: 0.70, 95% CI: 0.49-0.99) and of moderate exacerbation (HR: 0.63, 95% CI: 0.43-0.94). In contrast, compared with sulfonylureas, DPP-4 inhibitors were associated with a modest decreased incidence of severe (4.6 vs 5.1 per 100 person-years, respectively; HR: 0.91, 95% CI: 0.82-1.02) or moderate exacerbation (HR: 0.93, 95% CI: 0.82-1.07).

Conclusions: In this population-based study, the use of GLP-1 RAs was associated with a reduced risk of severe and moderate exacerbations when compared with the use of sulfonylureas in patients with COPD and type 2 diabetes. In contrast, DPP-4 inhibitors were not clearly associated with a decreased risk of COPD exacerbations.