Topical Recombinant Human Epidermal Growth Factor for Diabetic Foot Ulcers: A Meta-Analysis of Randomized Controlled Clinical Trials

Diabetic foot ulcer and its complications are becoming more and more serious problems threatening people's health. In the last decade, multiple growth factors and their combined applications have shown potentials in promoting the healing process of diabetic foot ulcers. The purpose of this study is to perform a meta-analysis of the efficacy and safety of topical recombinant human epidermal growth factor (rhEGF) on the treatment of diabetic foot ulcers. As of November 30, 2018, we had conducted a comprehensive review of PubMed, EMBASE, Cochrane Library databases, and Web of Science. Seven randomized controlled trials (RCTs) that involved 610 participants were included in this review. The pooled results showed that topical rhEGF could significantly promote the healing of diabetic foot ulcers (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.30 to 1.83; I-2 = 18%). Topical application of rhEGF could promote ulceration healing of diabetic feet of Wagner grade 1 or 2 significantly (RR, 1.61; 95% CI, 1.32 to 1.97; I-2 = 0%), and intralesional injection of rhEGF appeared to promote the healing of more severe ulcers (RR, 2.06, 95%, CI 0.35 to 12.22; I-2 = 50%). However, patients developed more shivering (RR, 4.67; 95% CI, 1.39 to 15.71; I-2 = 0%), nauseas/vomiting (RR, 2.18; 95% CI, 0.72 to 6.55; I-2 = 0%) in the group of intralesional injection of rhEGF compared with the control group, although these symptoms were not found with the topical application of rhEGF. No serious complications were found associated with topical rhEGF. Topical rhEGF treatment of diabetic foot ulcers has showed a broad application prospect, yet more relevant well-designed RCTs are needed in the future.