Effectiveness of hyaluronic acid and its derivatives on diabetic foot ulcer: a systematic review and meta-analysis.

Background: In this study, we aim to evaluate the effects of hyaluronic acid and its derivatives on wound healing in diabetic foot ulcer. Methods: The electronic databases included PubMed, BIOSIS, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar internet. The final search was updated on Aug 31, 2024. We assessed eligible studies that comparing the effects of hyaluronic acid and its derivatives with other dressings on wound healing in diabetic foot ulcer. The primary outcomes included the rate of ulcers completely healed, time to healing and adverse event. The standard mean differences (SMDs) or the odds ratios (ORs) were calculated for continuous or dichotomous data, respectively. Data were analyzed by using the Cochrane Collaboration's RevMan 5.0 software. Results: We assessed each included study with the Cochrane 'Risk of bias' tool. Seven RCTs involving 444 patients and 456 ulcers were included in our study. Hyaluronic acid may improve the complete ulcer healing rate (OR 3.92, 95% CI 1.74 to 8.81, P = 0.02, I2 = 62%) and shorten the time to ulcer healing (SMD = -0.83, 95% CI -1.13 to -0.53, P = 0.24, I2 = 28%), with no increasing the incidence of adverse events (OR = 0.79, 95% CI 0.46 to 1.35, P = 0.31, I2 = 16%). Conclusion: In conclusion, HA and its derivatives could be a potentially beneficial therapy for DFU treatment that promotes the complete ulcer healing rate, shortens healing time, without increasing incidence of adverse events. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024588743, identifier CRD42024588743.