Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysis

ObjectiveThis study aimed to evaluate the efficacy and safety of different growth factors (GFs) in the treatment of diabetic foot ulcers (DFUs) through a network meta-analysis.MethodsA systematic search was conducted in PubMed, Embase, The Cochrane Library, and Web of Science to identify randomized...

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Main Authors: Jianzhou Tian, Guanghui Yao, Tian Tian, Xinlin Li, Shaoru Li, Chengda Wu, Saisheng Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1614597/full
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author Jianzhou Tian
Guanghui Yao
Guanghui Yao
Guanghui Yao
Guanghui Yao
Tian Tian
Xinlin Li
Shaoru Li
Chengda Wu
Saisheng Zhang
author_facet Jianzhou Tian
Guanghui Yao
Guanghui Yao
Guanghui Yao
Guanghui Yao
Tian Tian
Xinlin Li
Shaoru Li
Chengda Wu
Saisheng Zhang
author_sort Jianzhou Tian
collection DOAJ
description ObjectiveThis study aimed to evaluate the efficacy and safety of different growth factors (GFs) in the treatment of diabetic foot ulcers (DFUs) through a network meta-analysis.MethodsA systematic search was conducted in PubMed, Embase, The Cochrane Library, and Web of Science to identify randomized controlled trials (RCTs) comparing GFs with standard of care (SOC) or comparing different GFs for the treatment of DFU. Two independent reviewers screened the studies, extracted data, and assessed the quality of the included literature according to predefined inclusion and exclusion criteria. A network meta-analysis was performed using R software. Relative risk (RR) was used as the effect measure for dichotomous outcomes, and mean difference (MD) was used for continuous outcomes.ResultsA total of 51 RCTs, involving 3,401 patients with DFUs and six different types of GFs, were included. The network meta-analysis revealed that, compared with SOC, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and platelet-rich plasma (PRP) significantly improved the healing rate. EGF and PRP also significantly reduced healing time, while PDGF significantly reduced ulcer area. Moreover, PRP was associated with a significant reduction in the incidence of adverse events (AEs) and amputation rates. In terms of ranking: For healing rate, the top three GFs were EGF, vascular endothelial growth factor (VEGF), and granulocyte colony-stimulating factor (G-CSF). For healing time, EGF, PRP, and fibroblast growth factor (FGF) ranked the highest. For ulcer area reduction, PDGF, EGF, and PRP were the top-ranking interventions. Regarding AEs, PRP, PDGF, and FGF showed the most favorable safety profiles. For amputation rate, PRP, G-CSF, and PDGF were ranked the highest.ConclusionAlmost all GFs outperformed SOC in terms of healing rate, healing time, and ulcer area reduction. Compared to SOC, EGF, PDGF, and PRP significantly improved healing rates; EGF and PRP significantly reduced healing time; and PDGF significantly decreased ulcer area. Among them, EGF may be the most effective GF. Except for VEGF, which significantly increased AEs, other GFs did not show a significant increase in AEs compared to SOC. PRP had the lowest amputation rate and incidence of AEs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251035765
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spelling doaj-art-3c01863cdd2e4edba1d8da21089f63e82025-08-20T02:20:40ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-06-011610.3389/fendo.2025.16145971614597Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysisJianzhou Tian0Guanghui Yao1Guanghui Yao2Guanghui Yao3Guanghui Yao4Tian Tian5Xinlin Li6Shaoru Li7Chengda Wu8Saisheng Zhang9Department of Burn and Plastic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaReproductive Medicine Center, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaHubei Clinical Research Center for Reproductive Medicine, Shiyan, Hubei, ChinaShiyan Key Laboratory of Reproduction and Genetics (Renmin Hospital, Hubei University of Medicine), Shiyan, Hubei, ChinaBiomedical Engineering College, Hubei University of Medicine, Shiyan, ChinaDepartment of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaDepartment of Burn and Plastic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaDepartment of Burn and Plastic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaDepartment of Burn and Plastic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaDepartment of Burn and Plastic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, ChinaObjectiveThis study aimed to evaluate the efficacy and safety of different growth factors (GFs) in the treatment of diabetic foot ulcers (DFUs) through a network meta-analysis.MethodsA systematic search was conducted in PubMed, Embase, The Cochrane Library, and Web of Science to identify randomized controlled trials (RCTs) comparing GFs with standard of care (SOC) or comparing different GFs for the treatment of DFU. Two independent reviewers screened the studies, extracted data, and assessed the quality of the included literature according to predefined inclusion and exclusion criteria. A network meta-analysis was performed using R software. Relative risk (RR) was used as the effect measure for dichotomous outcomes, and mean difference (MD) was used for continuous outcomes.ResultsA total of 51 RCTs, involving 3,401 patients with DFUs and six different types of GFs, were included. The network meta-analysis revealed that, compared with SOC, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and platelet-rich plasma (PRP) significantly improved the healing rate. EGF and PRP also significantly reduced healing time, while PDGF significantly reduced ulcer area. Moreover, PRP was associated with a significant reduction in the incidence of adverse events (AEs) and amputation rates. In terms of ranking: For healing rate, the top three GFs were EGF, vascular endothelial growth factor (VEGF), and granulocyte colony-stimulating factor (G-CSF). For healing time, EGF, PRP, and fibroblast growth factor (FGF) ranked the highest. For ulcer area reduction, PDGF, EGF, and PRP were the top-ranking interventions. Regarding AEs, PRP, PDGF, and FGF showed the most favorable safety profiles. For amputation rate, PRP, G-CSF, and PDGF were ranked the highest.ConclusionAlmost all GFs outperformed SOC in terms of healing rate, healing time, and ulcer area reduction. Compared to SOC, EGF, PDGF, and PRP significantly improved healing rates; EGF and PRP significantly reduced healing time; and PDGF significantly decreased ulcer area. Among them, EGF may be the most effective GF. Except for VEGF, which significantly increased AEs, other GFs did not show a significant increase in AEs compared to SOC. PRP had the lowest amputation rate and incidence of AEs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251035765https://www.frontiersin.org/articles/10.3389/fendo.2025.1614597/fulldiabetic foot ulcergrowth factorsstandard of carerandomized controlled trialnetwork meta-analysis
spellingShingle Jianzhou Tian
Guanghui Yao
Guanghui Yao
Guanghui Yao
Guanghui Yao
Tian Tian
Xinlin Li
Shaoru Li
Chengda Wu
Saisheng Zhang
Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysis
Frontiers in Endocrinology
diabetic foot ulcer
growth factors
standard of care
randomized controlled trial
network meta-analysis
title Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysis
title_full Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysis
title_fullStr Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysis
title_full_unstemmed Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysis
title_short Comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers: an updated network meta-analysis
title_sort comparison of the efficacy and safety of different growth factors in the treatment of diabetic foot ulcers an updated network meta analysis
topic diabetic foot ulcer
growth factors
standard of care
randomized controlled trial
network meta-analysis
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1614597/full
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