Epidermal Growth Factor Outperforms Placebo in the Treatment of Diabetic Foot Ulcer: A Meta-Analysis

Background: Diabetic foot ulcers (DFUs) are a life-threatening ailment caused by diabetes. Several growth factors, as well as their various combinations, have shown promising effect in aiding diabetic foot ulcer healing. However, contradictory or paradoxical results are often available, and debates about this issue are ongoing. Therefore, a comprehensive meta-analysis was performed to compare the efficacy and safety of epidermal growth factor (EGF) and placebo in healing diabetic foot ulcers. Methods: The database search included relevant English literature from Cochrane Library, PubMed, Google Scholar, Elsevier, and EMBASE that was published between 2009 and 2021. Inclusion criteria included type 1 and 2 diabetic patients with foot wounds focusing on complete healing rate. Exclusion criteria included combined therapy, non-human studies, reviews, and protocols. To assess the quality of each study, biases regarding random sequence generation, allocation concealment, participant and personnel blinding, outcome assessment blinding and incomplete outcome data were thoroughly identified. Results: Eight randomized control trials comprising 620 patients (337 in EGF group, 283 in placebo group), were included in this meta-analysis. EGF achieved a significantly higher complete healing rate than placebo after four weeks of treatment, with relative risk (RR): 3.04 (0.50, 18.44) and heterogeneity (Chi2 = 6.46, df = 2 (P = 0.04) I2 = 69 %). Notably, the healing frequency in the placebo group was 17%, whereas the healing frequency in the epidermal growth factor group was 34%. Likewise, after eight weeks of treatment, the relative risk and heterogeneity were RR: 2.59 (1.42, 4.72) and (Chi2 =7.92, df= 4 (p= 0.09): I2= 49%), respectively. Moreover, the risk ratio at 12 weeks was RR: 1.01 (0.42, 2.46), and heterogeneity was (Chi2 =8.55, df= 2 (p= 0.01): I2= 77%). Conclusions: Our findings indicate that EGF significantly promotes wound healing, and could be recommended as an effective and safe treatment for DFUs.