Effect of SGLT-2 inhibitors on COPD exacerbations in individuals with type 2 diabetes: A meta-analysis and Bayesian sensitivity analysis.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) and Type 2 diabetes mellitus (T2DM) frequently coexist, amplifying morbidity, mortality, and healthcare costs. COPD exacerbations are more frequent and severe in T2DM patients, necessitating therapies addressing both conditions. This systematic review and meta-analysis evaluates the impact of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on COPD exacerbations in T2DM patients.

Methods: Following PRISMA guidelines, we searched PubMed, Embase, and Web of Science until March 2025 for studies assessing SGLT-2i effects on COPD exacerbations in T2DM. Eligible studies included adults with T2DM-COPD overlap, reporting exacerbation outcomes. A random-effects meta-analysis and Bayesian hierarchical models were employed, with sensitivity and subgroup analyses.

Results: Seven studies (449,530 participants) were included. SGLT-2i use reduced COPD exacerbation risk by 39% (pooled HR: 0.609, 95% CI: 0.431-0.858), with Bayesian analysis supporting a 31% reduction (HR: 0.64, 95% CrI: 0.40-0.88). Subgroup analyses showed superior efficacy vs DPP-4 inhibitors (HR: 0.618, 95% CI: 0.462-0.827) and sulfonylureas (HR: 0.620, 95% CI: 0.526-0.731), and modest benefit over GLP-1RAs (HR: 0.940, 95% CI: 0.890-0.992). Severe exacerbation reduction was non-significant (HR: 0.676, 95% CI: 0.340-1.344). Heterogeneity was high (I² ≥ 97.9%), but sensitivity analyses confirmed robustness.

Conclusions: SGLT-2 inhibitors significantly reduce COPD exacerbations in T2DM patients, offering dual cardiometabolic and respiratory benefits. Their superiority over other antidiabetic agents supports prioritization in high-risk T2DM-COPD populations. Further trials are needed to validate effects on severe exacerbations and elucidate mechanisms.