(SLC-003) Sodium-Glucose Co-Transporter-2 Inhibitor Use and Risks of Exacerbation and Pneumonia in Patients with Chronic Obstructive Pulmonary Disease and Diabetes Mellitus: A Population-Based Cohort Study

Background: Chronic obstructive pulmonary disease (COPD) poses a significant health burden. Preventing exacerbations and pneumonia is crucial in managing COPD. Despite various treatments, COPD remains a leading cause of morbidity and mortality, underscoring the need for drug repurposing in its management. In vitro and ex vivo studies suggest sodium-glucose co-transporter-2 inhibitors (SGLT2i) may benefit lung function, but real-world evidence remains scant and is limited by study constraints, such as including COPD-asthma overlap patients and unassessed pneumonia risk.

Objectives: To assess whether SGLT2i use lowers risks of severe exacerbation and severe pneumonia in patients with COPD and diabetes mellitus.

Methods: This active-comparator, new-user, 1:1 propensity score-matched cohort study analyzed the Taiwan nationwide health insurance claims data from 2009 to 2022. We first identified a base cohort of patients with COPD and diabetes mellitus from 2016/05/01 to 2021/12/31, among whom patients initiating SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP-4i) were identified as the study cohort. DPP-4i were chosen as the active comparator mainly due to the lack of their reported effects on the risk of COPD exacerbations. Primary outcomes included first occurrence of severe COPD exacerbations and severe pneumonia requiring hospitalization. Secondary outcomes were the annual rate of severe exacerbations, first event of moderate-to-severe exacerbations, respiratory-related mortality, and all-cause mortality. Cox proportional hazards models and generalized linear mixed models (log link, Poisson distribution) estimated hazard ratios (HRs) for time-to-first outcomes and incidence rate ratios (IRRs) for the annual exacerbation rate, both with 95% confidence intervals (CIs).

Results: The study cohort included 5,391 COPD and diabetic patients initiating SGLT2i and 5,391 matched new DPP4i users (mean age, 69.1 years; 72% male). SGLT2i use was associated with a 16% reduced risk of severe COPD exacerbation compared with DPP4i (HR, 0.84; 95% CI, 0.74-0.95). Similar protective associations were observed when comparing SGLT2i with DPP4i for the annual rate of severe COPD exacerbations (IRR, 0.85; 95% CI, 0.72-0.99) and the risk of moderate-to-severe exacerbation (HR, 0.84; 95% CI, 0.77-0.92), as well as for severe pneumonia (HR, 0.64; 95% CI, 0.54-0.75), respiratory-related mortality (HR, 0.44; 95% CI, 0.36-0.55), and all-cause mortality (HR, 0.46; 95% CI, 0.40-0.53).

Conclusions: This nationwide cohort study found that SGLT2i use, compared to DPP4i, was associated with lower risks of severe COPD exacerbation, pneumonia, and mortality in patients with COPD and diabetes, suggesting a potential clinical benefit of SGLT2i in improving COPD outcomes.