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Novel antidiabetic agents and the risk of respiratory diseases: a systematic review and meta-analysis of 27 randomized controlled trials

Yu Z, Gu B, Zhang J, Jin W, Wan H, Jin W

Frontiers in medicine, 2025

202,727 participants · 1 citation

Abstract

Introduction: Patients with type 2 diabetes (T2D) are at increased risk of respiratory diseases, but the effects of novel glucose-lowering drugs on respiratory diseases remain unclear.

Method: We conducted a systematic review and meta-analysis of 27 large randomized controlled trials (202,727 participants) assessing sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is). Prespecified outcomes included pneumonia, bronchitis, chronic obstructive pulmonary disease (COPD), pulmonary edema, pulmonary embolism, respiratory failure, and asthma. Pairwise and network meta-analyses were performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs). This review was prospectively registered in PROSPERO (CRD420251158592).

Result: Compared with placebo, SGLT2is significantly reduced the risk of six respiratory diseases: pneumonia (OR 0.84, 95% CI 0.77-0.92), bronchitis (OR 0.59, 95% CI 0.44-0.79), COPD (OR 0.76, 95% CI 0.64-0.90), pulmonary edema (OR 0.51, 95% CI 0.39-0.67), respiratory failure (OR 0.77, 95% CI 0.64-0.91), and asthma (OR 0.55, 95% CI 0.38-0.85). Benefits were broadly consistent in patients with and without T2D. GLP-1RAs were neutral in T2D but reduced pneumonia, respiratory failure, and asthma risk in obese populations. DPP-4is were largely neutral but increased asthma risk (OR 1.70, 95% CI 1.03-2.82).

Conclusion: SGLT2 inhibitors showed robust respiratory…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 202,727 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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