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

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.