Reassessing the risk-modifying effects of novel antidiabetic agents on asthma-COPD overlap syndrome: a dose-stratified network meta-analysis of 316,832 adults from 128 randomised trials.
meta_analysis · Level I
Where this comes from
- Record sourced from PubMed, PMID 42376494.
- Also identified by DOI 10.1016/j.eclinm.2026.104026 and PMC identifier 13311999.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) accounts for 15-25% of chronic obstructive airway disease and is linked to frequent exacerbations and excess mortality. Newer glucose-lowering drugs may affect respiratory outcomes, but agent-level and dose-specific effects on ACOS are uncertain. We searched PubMed, Embase, Cochrane CENTRAL, Web of Science, ClinicalTrials.gov, ClinicalKey, ScienceDirect, and ProQuest from inception to April 03, 2026, with an initial search on Dec 12, 2024. Eligible studies were randomised controlled trials in adult participants receiving eligible glucose-lowering therapies and systematically recording ACOS-related, asthma, or COPD events during follow-up. Trials compared dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and other eligible antidiabetic regimens against standard care and/or placebo control. Risk ratios (RRs) with 95% CIs were estimated relative to this control group for ACOS, asthma, and COPD outcomes. Heterogeneity was assessed using tau-squared and <i>I</i> <sup><i>2</i></sup> statistics, and small-study effects/publication bias were assessed using comparison-adjusted funnel plots and Egger's regression. Outcome was trial-reported ACOS-related respiratory events. This study is registered with PROSPERO, CRD42024626613. Canagliflozin (RR 0.62, 95% CI 0.40-0.97), empagliflozin (0.70, 0.51-0.95), dapagliflozin (0.76, 0.63-0.92), and injectable semaglutide (0.64, 0.49-0.84) were associated with lower ACOS risk than control. Dose-stratified analyses suggested stronger associations for selected regimens, with signals more evident in participants with diabetes. Dapagliflozin was associated with lower asthma risk, whereas canagliflozin, empagliflozin, and injectable semaglutide were associated with lower COPD risk. Saxagliptin was associated with higher asthma risk (2.09, 1.01-4.33). No major heterogeneity, inconsistency, or small-study effects were detected. Respiratory associations of newer glucose-lowering therapies were heterogeneous and agent specific. Selected SGLT2 inhibitors and injectable semaglutide were associated with lower ACOS-related risk, whereas saxagliptin may warrant caution in people prone to asthma. These findings support further prospective evaluation. Taiwan National Science and Technology Council.