SGLT-2 inhibitors, GLP-1 receptor agonists lower COPD exacerbation risk

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with a reduced risk of moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes and active COPD, according to results of a comparative effectiveness research study.

Researchers assessed data from three propensity score-matched cohort studies in patients ages 40 years or older with type 2 diabetes and COPD who initiated treatment with SGLT-2 inhibitors or DPP-4 inhibitors (27,991 pairs), GLP-1 receptor agonists or DPP-4 inhibitors (32,107 pairs), and SGLT-2 inhibitors or GLP-1 receptor agonists (36,218 pairs). The primary outcome was first occurrence of a moderate or severe COPD exacerbation, which researchers defined as a filled prescription for oral glucocorticoids in association with an outpatient COPD visit or hospitalization for COPD. Findings were published by JAMA Internal Medicine on Feb. 10.

A total of 393,847 patients were included in the study (mean age, approximately 70 years) and median follow-up was 145 days. During this period, the risk of moderate or severe COPD exacerbation was lower among those treated with SGLT-2 inhibitors compared with DPP-4 inhibitors (9.26 vs. 11.4 per 100 person-years; hazard ratio [HR], 0.81 [95% CI, 0.76 to 0.86]). Risk of COPD exacerbation was also lower among those treated with GLP-1 receptor agonists versus DPP-4 inhibitors (9.89 vs. 11.49 per 100 person-years; HR, 0.86 [95% CI, 0.81 to 0.91]). Minimal differences were seen between SGLT-2 inhibitors and GLP-1 receptor agonists (9.47 vs. 10.00 per 100 person-years; HR, 0.94 [95% CI, 0.89 to 1.00]). Results were consistent across various subgroup and sensitivity analyses.

Overall, the data indicate a 19% lower risk of moderate or severe COPD exacerbations and a 29% reduction in severe exacerbations with SGLT-2 inhibitors compared with DPP-4 inhibitors, the study authors calculated. Similarly, GLP-1 receptor agonists showed a 14% lower risk of moderate or severe exacerbations and an 18% reduction in severe exacerbations compared with DPP-4 inhibitors, the researchers wrote. SGLT-2 inhibitors were associated with a 6% lower risk of moderate or severe COPD exacerbations and a 7% reduction in severe exacerbations compared with GLP-1 receptor agonists.

Limitations to the study include potential residual confounding, and use of claims data may have caused outcome misclassification. The researchers noted that the short study follow-up time was primarily driven by high medication discontinuation rates (approximately 55%).

“These findings suggest that SGLT-2 [inhibitors] and GLP-1 [receptor agonists] may be preferable to DPP-4 [inhibitors] when deciding among glucose-lowering medications for patients with [type 2 diabetes] and active COPD,” they concluded.

An accompanying editorial said that target trial emulation (the methodology used by this study) can provide evidence to compliment randomized clinical trials, but the editorialists urged caution when interpreting the results and called for confirmation of the findings in randomized controlled trials. The editorialists also pointed out that patients who initiated treatment with DPP-4 inhibitors were older and more likely to be men, have frailty, and have more advanced COPD.