Impact of SGLT-2i on COPD exacerbations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

Abstract

Background

Chronic Obstructive Pulmonary Disease (COPD) and Type 2 Diabetes Mellitus (T2DM) often coexist, leading to compounded morbidity, mortality, and healthcare burden. COPD exacerbations significantly impact patients with T2DM, with increased frequency and severity. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have demonstrated promising benefits in managing both glycemic control and respiratory health. This systematic review and meta-analysis aim to assess the impact of SGLT-2 inhibitors on COPD exacerbations in T2DM patients.

Methods

We conducted a systematic review and meta-analysis following PRISMA guidelines, evaluating studies published until March 2025. A broad search strategy across PubMed, Embase, and Web of Science identified relevant studies comparing SGLT-2 inhibitors with other antidiabetic agents. Studies meeting predefined eligibility criteria, including those providing quantitative data on COPD exacerbation frequency and hospitalization rates, were included in the analysis.

Results

Eight studies involving 4,64,542 participants were included. The pooled hazard ratio (HR) for the impact of SGLT-2 inhibitors on COPD exacerbations was 0.646 (95 % CI: 0.470–0.889), demonstrating a 35 % decrease in exacerbations compared to other antidiabetic agents. SGLT-2 inhibitors demonstrated superior efficacy over DPP-4 inhibitors (HR: 0.618, 95 % CI: 0.462–0.827) and sulfonylureas (HR: 0.620, 95 % CI: 0.526–0.731). However, the reduction in severe exacerbations was not statistically significant (HR: 0.715, 95 % CI: 0.403–1.269). Subgroup analysis indicated that SGLT-2 inhibitors had a modest but significant advantage over GLP-1 receptor agonists (HR: 0.940, 95 % CI: 0.890–0.993).

Conclusions

SGLT-2 inhibitors significantly reduce COPD exacerbations in T2DM patients, offering dual benefits in managing both glycemic control and respiratory health. These findings support the integration of SGLT-2 inhibitors into treatment regimens for T2DM-COPD overlap. Further randomized controlled trials and long-term studies are needed to confirm the lasting efficacy and explore the underlying mechanisms.