6D-12 - Effects of GLP-1 receptor agonists on respiratory outcomes in type 2 diabetes patients: an inverse disproportionality analysis of FAERS data and systematic review with meta-analysis of Clinical trials

Background: Recent epidemiology studies have indicated that people with Type 2 Diabetes Mellitus (T2DM) have a higher prevalence of respiratory symptoms. GLP-1 receptor agonists (GLP-1RAs) mimic the action of GLP-1 levels in individuals with T2DM, which may be associated with improved respiratory outcomes.

Objectives: To assess the effects of GLP-1RAs on respiratory outcomes in patients with T2DM

Methods: A retrospective case/non-case inverse disproportionality analysis was performed using spontaneous reports of respiratory outcomes associated with GLP-1RAs from the FDA Adverse Event Reporting System (FAERS). An inverse signal was defined as a Proportional Reporting Ratio (PRR) ≤ 1.0, upper limit of reporting odds ratio (UB ROR) 95% confidence interval (CI) <1, Number of cases(N)≥3 and information Component (IC025) < 0. Additionally, an extensive search of PubMed, EMBASE, and Cochrane was conducted (from inception to 21st November 2024) to identify clinical trials comparing GLP-1RAs with placebo or active control that reported ≥1 respiratory outcome. Meta-analysis was performed using RevMan web to calculate risk ratios (RR) with 95% confidence intervals (CIs) using random-effects model. Certainty of evidence was assessed using the GRADE framework.

Results: FAERS data analysis revealed an inverse association for 50 respiratory outcomes, predominantly upper respiratory tract infection [Exenatide(PRR:0.5, UBROR:0.6, IC025:-1.5), Liraglutide(PRR:0.7, UBROR:0.9, IC025:-1.1), Dulaglutide(PRR:0.3, UBROR:0.4, IC025:-2.2) and Semaglutide(PRR:0.7, UBROR:0.9, IC025-1.0)]. Similar to that in meta-analysis, Semaglutide was associated with a low risk of upper respiratory tract infection [RR:0.64 (95%CI:0.51-08)] and respiratory thoracic and mediastinal disorder [RR:0.42 (95%CI:0.27- 0.66)]. Liraglutide reduce risk of sinusitis [RR:0.57 (95%CI:0.37-0.86)]. While dulaglutide increases the risk of upper respiratory disease [RR:1.51(95%CI:1.18- 1.94)]. GRADE assessment confirmed high-certainty evidence for semaglutide-associated respiratory, thoracic, and mediastinal disorders.

Conclusions: Both analyses consistently showed semaglutide's protective effect against upper respiratory infections, suggesting GLP-1RAs offer respiratory advantages over other diabetes treatments. However, other potential outcomes remain unstudied in trials. Current evidence, limited by few RCTs and safety data, requires validation through prospective and real-world studies.