Chronic obstructive pulmonary disease (COPD) is a common lung disease and the third most frequent cause of death worldwide. Type 2 diabetes (a disease caused by high blood sugar levels) increases health-problems in COPD. Thus, it is important to find new ways in improving the health of patients who have both type 2 diabetes and COPD. Laboratory research suggest that certain antidiabetic drugs, such as such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, may have beneficial effects in patients with COPD. However, very few studies have examined whether these drugs are able to prevent COPD exacerbations (sudden worsening of lung-related health) among patients with type 2 diabetes. Given the high prevalence of both COPD and type 2 diabetes, we will conduct a large, population-based cohort study using primary care, hospitalization, and death registry data from the United Kingdom. We will determine whether the use of incretin-based drugs (GLP-1-RAs and DPP-4 inhibitors), when compared with the use of sulfonylureas, antidiabetic drugs used in the same stage of the disease, is associated with a decreased risk of COPD exacerbation among patients with type 2 diabetes.
COPD and type 2 diabetes both highly prevalent diseases. While COPD increases the risk of diabetes, presence of diabetes results in frequent COPD exacerbations. Incretin-based drugs may reduce the frequency of exacerbations by reducing bronchial hyperresponsiveness. We will assemble a cohort of patients, at least 18 years of age, who initiated incretin-based drugs or sulfonylureas from 1 January 2007 (the year of availability of the comparator drugs in the United Kingdom) until 31 December 2019, with follow-up until March 31, 2020. Propensity scores will be computed to determine the predicted probability of treatment with GLP-1 RAs or DPP-4 inhibitors, separately, versus sulfonylureas. Cox proportional hazards models with propensity score fine stratification weighting will then be used to estimate hazard ratios of COPD exacerbation, separately for GLP-1 RAs and DPP-4 inhibitors. Secondary analyses will be conducted to determine whether there is a duration-response relation, association with individual drugs, and whether the association varies by age, sex, history of asthma, severity of dyspnoea at baseline, and predicted forced expiratory volume at one second. Given the relatively high mortality and morbidity associated with COPD among patients of type 2 diabetes, this study could have important implications for treatment guidelines, providing physicians, patients, and regulatory agencies with much-needed information.
The primary outcome will be the occurrence of the first episode of severe COPD exacerbation during the follow-up period. This will be defined as a hospitalization (identified using HES APC) with a COPD diagnosis in the primary position (definitions in Appendix 1).1, 2
There will be three secondary outcomes: (1) moderate COPD exacerbations (defined using a validated algorithm based on concomitant use of systemic corticosteroids and antibiotics)3, (2) count of moderate exacerbations, and (3) count of severe exacerbations (with events within 30 days of each other being counted as continuation of the same exacerbation episode for the count-based analyses).
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Pierre Ernst - Collaborator - McGill University
Richeek Pradhan - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Sally Lu - Collaborator - McGill University
HES Admitted Patient Care