Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Foot Ulcer Healing: A Meta-Analysis of Randomized Clinical Trials

Background Diabetic foot ulcers (DFUs) are a serious complication of diabetes, often leading to amputations and high healthcare costs. Dipeptidyl peptidase-4 (DPP-4) inhibitors may help wound healing by enhancing angiogenesis. This study aimed to evaluate the efficacy of DPP-4 inhibitors in DFUs healing. Methods This systematic review and meta-analysis followed PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing DPP-4 inhibitors with standard care or placebo were searched in PubMed, Scopus, Web of Science, and Cochrane Library up to October 1, 2025. Relative risk (RR) and mean difference (MD) were pooled using a random-effect model . Results Four RCTs with 285 patients were included. DPP-4 inhibitors significantly increased complete ulcer healing (RR = 1.63, 95% CI 1.30-2.06, P < .0001) and shortened healing time (MD = −10.72 days, 95% CI −14.61 to −6.84, P < .00001). Ulcer size was also reduced (MD = −2.36 cm 2 , 95% CI −2.95 to −1.77, P < .00001). Side effects were rare and similar between groups. Conclusion Treatment with DPP-4 inhibitors improves DFU healing outcomes compared to the control group. This finding is limited to the number of included studies and the small sample size. Future randomized clinical trials are warranted to provide more robust results.