GLP-1 RAs, SGLT2 Inhibitors Could Reduce COPD Exacerbations in People with Diabetes

Laurent Azoulay, PhD

Results of a study from investigators at McGill University and other institutions in Montreal, Canada suggest use of GLP-1 receptor agonists and SGLT2 inhibitors could play a role in management of chronic obstructive pulmonary disease (COPD) in people with diabetes.

Although most of the recent attention surrounding newer antihyperglycemic agents have centered around cardioprotective benefits, results of the current study suggest use of GLP-1 receptor agonist and SGLT2 inhibitors were associated with a reduced risk of severe exacerbations in people with COPD and type 2 diabetes compared to sulfonylureas, with investigators noting this association was not apparent for use of DPP-4 inhibitors.

“In this large population-based study, the use of GLP-1 receptor agonists and SGLT-2 inhibitors was associated with a lower risk of severe exacerbations among patients with type 2 diabetes and chronic obstructive pulmonary disease compared with sulfonylureas, whereas a risk reduction associated with DPP-4 inhibitor use, if any, was small,” wrote investigators.

Citing emerging research indicating GLP-1 receptors agonists, SGLT2 inhibitors, and DPP-4 inhibitors might provide pulmonary benefits, a team led by Laurent Azoulay, PhD, and colleagues from McGill University and the Lady Davis Institute at Jewish General Hospital in Canada, sought to assess whether use of either of the aforementioned agents was associated with a decreased risk of exacerbations of COPD in those with COPD and type 2 diabetes. With this in mind, Azoulay and colleagues designed a population-based cohort study with an active comparator, new user design leveraging data obtained from the United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases.

Using these data sources, which investigators noted contain approximately 2000 general practices and is representative of the general population of the UK with respect to age, sex, and ethnicity, investigates created 3 active comparator new user cohorts starting the study drugs or sulfonylureas. The first cohort included 1252 patients starting GLP-1 receptor agonists and 14259 starting sulfonylureas, the second cohort included 8731 patients starting DPP-4 inhibitors and 18204 starting sulfonylureas, and the third cohort included 2956 patients starting SGLT-2 inhibitors and 10841 starting sulfonylureas.

The primary outcome of interest was incidence of severe exacerbation of COPD, which was defined as a hospital admission for COPD, separately for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors. Risk of moderate exacerbation, which was defined as coprescription of an oral corticosteroid and an antibiotic along with an outpatient diagnosis of acute COPD exacerbation on the same day, served as a secondary outcome interest. Investigators pointed out risk of outcomes with each agent compared to use of sulfonylureas was estimated using Cox proportional hazards models with propensity score fine stratification.

Upon analysis, results indicated use of GLP-1 receptor agonists were associated with a 30% relative reduction in risk of severe exacerbation (3.5 vs 5.0 events per 100 person-years; HR, 0.70 [95% CI, 0.49-0.94]) and 37% reduction in risk of moderate exacerbation (HR, 0.63 [95% CI, 0.43-0.94]) as those receiving sulfonylureas. A reduction in risk was also observed for severe exacerbation among users of SGLT2 inhibitors compared with sulfonylureas (HR, 0.62 [95% CI, 0.48-0.81]), but this was not observed for moderate exacerbation (HR, 1.02 [95% CI, 0.83-1.27]) Investigators pointed out modest relative risk reductions were observed with use of DPP-4 inhibitors, but were associated with wide confidence intervals that included the null value.

“Further research, including confirmatory randomized controlled trials, will be needed to investigate the potential of GLP-1 receptor agonists and SGLT-2 inhibitors as a therapeutic option in patients with type 2 diabetes and chronic obstructive pulmonary disease,” investigators added.

This study, “Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study,” was published in The BMJ.