GLP-1 receptor agonists and SGLT-2 inhibitors best sulfonylureas in reducing COPD exacerbations in diabetes patients

A new study from Canada found that glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT-2) inhibitors were associated with a reduced risk of severe exacerbations compared with sulfonylureas in patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2 DM).  

GLP-1 receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and SGLT-2 inhibitors are commonly prescribed novel antihyperglycemic drugs that have good cardiovascular effects. Recent studies showed that they have a good pulmonary effect too. Hence researchers conducted a large population-based cohort study to determine whether GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors, separately, are associated with a decreased risk of COPD exacerbation among patients with COPD and T2 DM, compared with sulfonylureas.  

Data from The United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases were used for the study. New user cohorts of patients having T2 DM and starting the study drugs (GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT-2 inhibitors) or sulfonylureas with a history of chronic obstructive pulmonary disease were taken for the study. In the first cohort 1252 patients started GLP-1 receptor agonists and 14 259 started sulfonylureas, the second cohort included 8731 patients starting DPP-4 inhibitors and 18 204 starting sulfonylureas, and the third cohort included 2956 patients starting SGLT-2 inhibitors and 10 841 starting sulfonylureas. 

All three comparators were separately analyzed using the Cox proportional hazards models with propensity score fine stratification weighting to estimate hazard ratios and 95% confidence intervals of severe exacerbation of the chronic obstructive pulmonary disease. Decreased risk of exacerbations was also assessed. 

Results: 

Compared with Sulphonylureas: 

Thus, GLP-1 receptor agonists and SGLT-2 inhibitors were associated with a lower risk of severe exacerbations among patients with type 2 diabetes and chronic obstructive pulmonary disease compared with sulfonylureas and the risk reduction associated with DPP-4 inhibitor use was small. 

Take-home points: 

• GLP-1 receptor agonists were associated with a lower risk of severe and moderate COPD exacerbations among patients with type 2 diabetes and COPD, compared with sulfonylureas. 
• DPP-4 inhibitors generated very modest risk reductions in COPD exacerbations, but these were associated with wide confidence intervals that included the null value. 
• SGLT-2 inhibitors were associated with a decreased risk of severe COPD exacerbations but not moderate exacerbations. 

Further reading: Pradhan R, Lu S, Yin H, et al. Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study. BMJ. 2022;379:e071380. Published 2022 Nov 1. doi:10.1136/bmj-2022-071380