SGLT-2 Inhibitors and the Risk of Chronic Obstructive Pulmonary Disease Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease Patients

<b>Rationale:</b> Patients with chronic obstructive pulmonary disease (COPD) are susceptible to acute exacerbations, cardiovascular disease, and premature death. <b>Objectives:</b> To compare the risk of COPD exacerbation, cardiovascular diseases, and mortality between SGLT-2 (sodium-glucose cotransporter-2) inhibitor use and nonuse in patients with type 2 diabetes mellitus (T2DM) and COPD. <b>Methods:</b> The study included 299,168 patients with diagnoses of T2DM and COPD in the National Health Insurance Research Database from January 1, 2009, to December 31, 2020. Cox proportional hazards models were used to examine the relative hazard of the primary outcome (a composite of hospitalization for COPD, noninvasive positive-pressure ventilation [NIPPV], invasive mechanical ventilation, and all-cause mortality) and secondary outcomes: major adverse cardiovascular events, hospitalization for COPD, NIPPV, invasive mechanical ventilation, lung cancer, and mortality between SGLT-2 inhibitor users and nonusers. We used propensity score matching to select 1,288 pairs of SGLT-2 inhibitor users and nonusers. <b>Results:</b> In the matched cohorts, SGLT-2 inhibitor use was associated with a significantly lower risk of the primary outcome (multivariable-adjusted hazard ratio [aHR], 0.79 [95% confidence interval (CI), 0.67-0.93]), NIPPV (aHR, 0.48 [95% CI, 0.27-0.87]), hospitalization for COPD (aHR, 0.82 [95% CI, 0.69-0.98]), and mortality (aHR, 0.64 [95% CI, 0.43-0.95]), than SGLT-2 inhibitor nonuse. Subgroup and dose-response analyses showed that SGLT-2 inhibitor use was associated with a significantly lower risk of mortality, NIPPV, and hospitalization for COPD (<i>P</i> < 0.05) than nonuse of SGLT-2 inhibitors. <b>Conclusions:</b> This population-based cohort study showed that SGLT-2 inhibitor use was associated with a lower risk of the primary outcome, COPD exacerbations, ventilator support, and mortality than SGLT-2 inhibitor nonuse in patients with T2DM and COPD. SGLT-2 inhibitors may have a role in treating patients with COPD and diabetes.