2732-LB: GLP-1 Receptor Agonists and Diabetic Foot Ulcer Risk: A Meta-analysis

Introduction and Objective: GLP-1 RAs confer cardiovascular and metabolic benefits, but their specific impact on DFU risk remains unclear. This meta-analysis systematically evaluated the association between GLP-1 RA therapy and incident DFUs, along with secondary outcomes of lower limb amputation (LLA), DFU-related hospitalization, and all-cause mortality in adults with T2DM. Methods: Following PRISMA guidelines, we searched PubMed, Embase, Cochrane Library, and Web of Science. Eligible studies included randomized controlled trials (RCTs) and observational cohort studies comparing GLP-1 RAs with other glucose-lowering therapies. Two reviewers independently screened studies, extracted data, and assessed bias using Cochrane RoB 2 (RCTs) and the Newcastle-Ottawa Scale (observational studies). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated via random-effects models. Subgroup analyses were stratified by treatment duration (≤400 vs. >400 days) and GLP-1 RA subtype (short- vs. long-acting). Sensitivity analyses and Egger’s test were performed to verify robustness. Results: We included 31 studies (18 RCTs and 13 cohorts) encompassing 826,412 T2DM patients were included. GLP-1 RA use was associated with an 19% lower risk of incident DFUs compared with controls (pooled HR = 0.81, 95% CI: 0.74-0.89, p < 0.001). Long-term use (>400 days) yielded stronger protection (HR = 0.74, 95% CI: 0.66-0.83) than short-term use (HR = 0.88, 95% CI: 0.79-0.98). GLP-1 RAs also significantly reduced LLA (HR = 0.72, 95% CI: 0.61-0.85), DFU-related hospitalization (HR = 0.78, 95% CI: 0.70-0.87), and all-cause mortality (HR = 0.85, 95% CI: 0.79-0.92; all p < 0.001). Heterogeneity was moderate (I² = 58%), and no significant publication bias was detected (Egger’s test p = 0.23). Conclusion: GLP-1 RA therapy significantly reduces the risk of DFUs and related complications in T2DM patients. These results support the clinical application of GLP-1 RAs among patients with DFU. Further large-scale trials are needed to verify causality and optimal regimens. Disclosure J. Yao: None. M. Wang: None. Y. Ding: None. G. Guo: None. L. Li: None. L. Zhang: None.