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Meta-Analysis
. 2025 Aug 11:13:e19809.
doi: 10.7717/peerj.19809. eCollection 2025.

Comparison of the efficacy of 12 interventions in the treatment of diabetic foot ulcers: a network meta-analysis

Xuyang Hu #  1   2 , Huixin Meng #  2 , Jiaru Liang  2 , Hang An  2 , Jiaqi Zhou  1 , Yuling Gao  1 , Chong You  2 , Zhenni Zhang  1 , Xiaoyang Gong  1 , Yong Liu  1   2
Affiliations
Meta-Analysis

Comparison of the efficacy of 12 interventions in the treatment of diabetic foot ulcers: a network meta-analysis

Xuyang Hu et al. PeerJ. .

Abstract

Objective: This study aimed to comprehensively compare the efficacy of 12 interventions for diabetic foot ulcer (DFU) using a network meta-analysis (NMA).

Methods: The NMA was conducted by PRISMA guidelines, and the protocol was registered in PROSPERO (CRD42023461811). PubMed, Web of Science, Cochrane Library, and Embase databases were systematically searched from inception to September 2023. Randomized controlled trials (RCTs) enrolling patients with DFU were included if they compared epidermal growth factor (EGF), platelet-derived growth factor (PDGF), platelet-rich plasma (PRP), stem cells (SC), low-frequency ultrasound (LFU), negative pressure wound therapy (NPWT), low-level laser therapy (LLLT), electric stimulation (ES), extracorporeal shockwave therapy (ESWT), amniotic membrane therapy (AMT), hyperbaric oxygen therapy (HBOT), and topical oxygen therapy (TOT) against standard of care (SOC) or placebo. The primary endpoint assessed was the wound healing rate. Secondary endpoints comprised wound healing time, percentage area reduction (PAR), and amputation rate. The surface under the cumulative ranking curve (SUCRA) was calculated to rank the efficacy of interventions.

Results: A total of 99 RCTs involving 7,356 patients were included. Among the 12 interventions analyzed, only LFU (OR = 2.20; 95% CI [0.99-4.91]) and ES (OR = 1.88; 95% CI [0.87-4.05]) did not demonstrate statistically significant improvements in ulcer healing rate compared with SOC. Based on SUCRA rankings, SC (SUCRA = 89.7%; OR = 5.71; 95% CI [2.64-12.34]) and AMT (SUCRA = 89.2%; OR = 5.11; 95% CI [3.12-8.37]) ranked highest in promoting ulcer healing, while LFU (29.4%) and SOC (10.4%) ranked lowest. Regarding wound healing time, AMT (MD = -26.91 days; 95% CI [-44.27 to -9.55]), PRP (MD = -21.65 days; 95% CI [-33.61 to -9.69]), and NPWT (MD = -16.79 days; 95% CI [-31.12 to -2.26]) significantly reduced healing durations compared to SOC. SUCRA rankings indicated that AMT (84.7%) and PRP (74.6%) ranked highest, while LFU (29.4%) and SOC (10.4%) remained lowest. Concerning PAR, LLLT (MD = 34.27; 95% CI [17.35-51.20]) and ESWT (MD = 27.50; 95% CI [11.00-44.00]) showed significant improvements over SOC, with LLLT (SUCRA = 93.9%) and ESWT (SUCRA = 84.0%) ranking highest, while SOC (21.0%) and TOT (18.3%) ranked lowest. For amputation rate, SC (OR = 0.12; 95% CI [0.03-0.55]) and HBOT (OR = 0.35; 95% CI [0.16-0.78]) significantly lowered the risk compared to SOC, with SUCRA rankings placing SC (79.9%) and PRP (73.2%) as most effective, while NPWT (26.4%) and SOC (9.9%) were least effective.

Conclusions: SC and AMT emerged as highly effective, demonstrating superior efficacy in improving healing rate compared to PDGF, ES, and HBOT. AMT also showed significant effects in shortening ulcer healing time. LLLT exhibited considerable effectiveness in reducing ulcer areas, and SC therapy was associated with reduced amputation rate.

Keywords: Amputation rate; Diabetic foot ulcers; Network meta-analysis; Percentage area reduction; Wound healing rate; Wound healing time.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. Flow chart of the study selection process.
A total of 1,981 records were identified from four databases. After removing duplicates and screening titles, abstracts, and full texts, 99 RCTs were included in the final analysis.
Figure 2
Figure 2. Network plots comparing different interventions for four outcomes.
(A) Wound healing rate; (B) wound healing time; (C) percentage area reduction (PAR); (D) amputation rate. The blue nodes represent individual interventions, with node size proportional to the sample size of each intervention. Lines between nodes indicate direct comparisons from included RCTs, with line thickness proportional to the number of studies performing each comparison.
Figure 3
Figure 3. Risk of bias graph of the included studies.
The proportion of studies rated as having low, unclear, or high risk of bias across seven domains is presented.
Figure 4
Figure 4. Forest plot of network meta-analysis results for wound healing rate.
Treatment effects are presented as odds ratios (ORs) with 95% confidence intervals (CIs).
Figure 5
Figure 5. Surface Under the Cumulative Ranking (SUCRA) values of different interventions for four outcomes.
(A) Wound healing rate; (B) wound healing time; (C) percentage area reduction (PAR); (D) amputation rate. Higher SUCRA values and larger areas under the curve indicate a greater probability that the intervention is more effective for the corresponding outcome.
Figure 6
Figure 6. Forest plot of network meta-analysis results for wound healing time.
Treatment effects are presented as mean differences (MDs) with 95% confidence intervals (CIs).
Figure 7
Figure 7. Forest plots of network meta-analysis results for (A) percentage area reduction (PAR) and (B) amputation rate.
Treatment effects are presented as mean differences (MDs) for PAR and odds ratios (ORs) for amputation rate, with 95% confidence intervals (CIs).
Figure 8
Figure 8. Forest plot of subgroup analysis based on follow-up duration.
Subgroup 1 included studies with follow-up ≤ 12 weeks, and subgroup 2 included studies with follow-up >12 weeks. Treatment effects are presented as odds ratios (ORs) with 95% confidence intervals (CIs).
Figure 9
Figure 9. Funnel plots of the study treatments.
(A) Wound healing rate; (B) Wound healing time; (C) Percentage area reduction (PAR); (D) Amputation rate.
See this image and copyright information in PMC

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