SGLT2 Inhibitors and Injectable Semaglutide Significantly Reduce Asthma-COPD Overlap Syndrome Risk

Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) affects 15-25% of chronic obstructive airway disease patients, leading to frequent exacerbations and increased mortality. Current standard-of-care often focuses on symptom management, but emerging evidence suggests that novel glucose-lowering drugs, particularly those impacting metabolic pathways, might influence respiratory outcomes. However, agent-level and dose-specific effects of these therapies on ACOS, asthma, and COPD risk have remained largely undefined, presenting a critical gap in understanding their broader clinical utility beyond Type 2 Diabetes Mellitus management.

This network meta-analysis aggregated data from 128 randomised controlled trials, encompassing 316,832 adults receiving various glucose-lowering therapies. Researchers systematically searched multiple databases for studies reporting ACOS-related, asthma, or COPD events. Eligible trials compared dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors against standard care or placebo. The primary endpoint was trial-reported ACOS-related respiratory events, with risk ratios (RRs) and 95% CIs estimated relative to control. Dose-stratified analyses were also performed to assess specific regimen impacts.

Several novel antidiabetic agents demonstrated significant reductions in ACOS risk. Canagliflozin was associated with a 38% lower ACOS risk (RR 0.62, 95% CI 0.40-0.97), empagliflozin with a 30% lower risk (RR 0.70, 95% CI 0.51-0.95), and dapagliflozin with a 24% lower risk (RR 0.76, 95% CI 0.63-0.92) compared to control.

Injectable semaglutide significantly reduced ACOS risk by 36% (RR 0.64, 95% CI 0.49-0.84), highlighting a substantial benefit. Dose-stratified analyses further suggested stronger associations for selected regimens, with these protective signals being more pronounced in participants with diabetes. Specifically, dapagliflozin was linked to a lower asthma risk, while canagliflozin, empagliflozin, and injectable semaglutide were associated with reduced COPD risk. Conversely, saxagliptin was associated with a concerning 109% higher asthma risk (RR 2.09, 95% CI 1.01-4.33), indicating potential adverse respiratory effects for this DPP-4 inhibitor. No major heterogeneity was observed across studies for most findings.