Incretin-based drugs and the prevention of exacerbations of chronic obstructive pulmonary disease among patients with type 2 diabetes mellitus

Date of Approval
Application Number
Technical Summary

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.

Health Outcomes to be Measured

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 - McGill University
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