Efficacy and safety of DPP-1 inhibitors in bronchiectasis: a GRADE-assessed meta-analysis of randomized controlled trials

Authors

Ahmed Emara, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Ameer Awashra, Department of Internal Medicine, An-Najah National University, Rafidia Street, Nablus, West Bank, P606, Nablus, Palestine. ameer.awashra7@gmail.com.
Mohamed Ellebedy, Faculty of Medicine, Sohag University, Sohag, Egypt.
Omar F. Abbas, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Ahmed Diaa, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Mohamed S. Elgendy, Faculty of Medicine, Tanta University, Tanta, Egypt.
Mohamed Emara, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Abdalhakim Shubietah, Advocate Health - MidwestFollow
Abdul Muhsen Abdeen, Department of Pulmonary and Critical Care Medicine, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV, 25701, USA.
Fadi Safi, Department of Pulmonary and Critical Care Medicine, University of Toledo, Toledo, OH, 43606, USA.

Recommended Citation

Emara A, Awashra A, Ellebedy M, et al. Efficacy and safety of DPP-1 inhibitors in bronchiectasis: a GRADE-assessed meta-analysis of randomized controlled trials. Respir Res. 2025;26(1):332. Published 2025 Nov 26. doi:10.1186/s12931-025-03407-2

Affiliations

Advocate Illinois Masonic Medical Center

Abstract

Background: Bronchiectasis is a chronic inflammatory airway disease characterized by frequent exacerbations and neutrophilic inflammation. Dipeptidyl peptidase-1 (DPP-1) inhibitors block neutrophil serine protease activation and represent a promising therapeutic approach. This meta-analysis aimed to evaluate the efficacy and safety of DPP-1 inhibitors in adults with bronchiectasis.

Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Central up to July 2025 for randomized controlled trials (RCTs) comparing DPP-1 inhibitors with placebo. Outcomes were pooled as risk ratios (RRs) or hazard ratio (HR) or mean differences (MDs) with 95% confidence intervals (CIs).

Prospero id: CRD420251116443.

Results: Four RCTs (n = 2,523 patients) were included. DPP-1 inhibitors significantly reduced the risk of having one exacerbation (RR 0.64; 95% CI: 0.52-0.78; P < 0.0001), severe exacerbations (RR 0.44; 95% CI: 0.21-0.92; P = 0.03), and increased the proportion of patients who remained exacerbation-free during treatment (RR 1.33; 95% CI: 1.13-1.57; P = 0.0008). Time to first exacerbation was delayed (HR 0.66; 95% CI: 0.50-0.88; P = 0.004). There was a significant improvement in respiratory symptom scores (MD 2.80; 95% CI: 1.10-4.50; P = 0.001), but no difference in FEV₁ post-bronchodilator or rates of 2 or ≥ 3 exacerbations (P > 0.05). DPP-1 inhibitors significantly reduced severe and serious adverse events without increasing overall adverse events, treatment discontinuations, or mortality.

Conclusion: DPP-1 inhibitors reduce exacerbation frequency, delay time to first exacerbation, and improve respiratory symptoms in bronchiectasis without compromising safety. These findings support their role as a potential disease-modifying therapy in bronchiectasis management. Further long-term studies are warranted to confirm their sustained clinical benefit.

Type

Article

PubMed ID

41299471