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Diabetes, Metabolic Syndrome and Obesity logoLink to Diabetes, Metabolic Syndrome and Obesity
. 2026 Sep 24;19:637616. doi: 10.2147/DMSO.S637616

Platelet-Rich Plasma for Diabetic Foot Ulcers: A Cross-Sectional Appraisal of Overlapping Meta-Analyses

Ying Du 1, Bolun Zhang 1, Xinxin Meng 1, Qiantai Gao 1, Xiyan Zhao 2,3,✉, Tianlin Wen 1,✉, Zhiwei Jia 1
PMCID: PMC13618608  PMID: 42808029

Abstract

Purpose

The treatment of diabetic foot ulcers (DFUs) remains challenging, and the benefits and safety of platelet-rich plasma (PRP) therapy are still debated. This study analyzed existing meta-analyses on PRP therapy for DFUs to identify the most reliable evidence source.

Methods

This cross-sectional appraisal was conducted according to PRISMA 2020 guidance. PubMed, Embase, and the Cochrane Library were searched from inception to May 20, 2026, for meta-analyses comparing PRP therapy with standard or conventional care for DFUs. Only meta-analyses based exclusively on randomized controlled trials (RCTs) were included. Methodological quality was assessed using AMSTAR, evidence level was classified according to the Oxford Levels of Evidence, and discordant findings were examined using the Jadad decision algorithm.

Results

Eleven meta-analyses were included in this study, all of which were categorized as Level II evidence. The AMSTAR scores ranged from 6 to 10 (median 8). The meta-analysis identified by the Jadad algorithm as the most robust source showed that autologous PRP improved complete ulcer healing rates (OR: 2.11; 95% CI: 1.55–2.86) and shortened complete healing time (MD: −19.04 days; 95% CI: −20.46 to −17.61) compared with standard care. Furthermore, the incidence of adverse events in PRP groups was not significantly different from that in standard care groups, and the results were robust in sensitivity analyses.

Conclusion

PRP is an effective adjunctive therapy for DFUs, with no statistically significant increase in reported adverse events. However, further large-scale, high-quality trials are needed to standardize PRP preparation and administration, and to establish optimal treatment protocols.

Keywords: platelet-rich plasma, diabetic foot ulcers, meta-analysis, Jadad decision algorithm, methodological quality

Graphical Abstract

A flowchart on PRP therapy for DFUs, showing problem, process and conclusion.

Introduction

Diabetes mellitus has become a major global public health challenge, with its prevalence continuing to rise rapidly worldwide.1 Among its numerous complications, diabetic foot ulcers (DFUs) are particularly serious because they are difficult to heal and are closely associated with infection, hospitalization, lower-extremity amputation, and increased mortality.2,3 The development of DFUs is usually multifactorial, involving peripheral neuropathy, peripheral arterial disease, impaired immune function, infection, and delayed tissue repair.2,4 In addition to causing substantial physical and psychological suffering for patients, DFUs also impose a considerable economic burden on healthcare systems.3,5 Given their high prevalence, prolonged disease course, and potential for severe complications, improving the management of DFUs remains an important clinical priority.2,6

Standard care for DFUs is based on a multidisciplinary treatment strategy, including optimization of glycemic control, wound debridement, infection control, pressure off-loading, appropriate dressings, vascular assessment, and revascularization when necessary.2,7–9 These approaches are essential and remain the foundation of DFU treatment.2,7–9 However, standard care may not achieve satisfactory healing in all patients, especially in those with chronic, complex, or refractory ulcers.2,10 Conventional dressings are mainly used to protect the wound, absorb exudate, and help maintain a moist wound environment, but they may have limited capacity to actively modulate impaired biological processes underlying diabetic wound healing.2,10,11 As a result, many patients experience delayed wound closure, recurrent ulceration, or progression to severe complications.2,3

In this context, regenerative therapies have attracted increasing attention as potential adjunctive treatments for DFUs.10,12 Platelet-rich plasma (PRP) is one of the most widely investigated biological therapies in this field.12–14 PRP is prepared from autologous blood and contains a concentrated number of platelets, which can release various growth factors, cytokines, and bioactive mediators after activation.12,15 These components may contribute to wound repair by enhancing angiogenesis, stimulating fibroblast proliferation, promoting extracellular matrix remodeling, modulating inflammation, and accelerating granulation tissue formation.12,15 Owing to these biological effects, PRP has been proposed as a promising treatment option for diabetic wounds, particularly when standard care alone is insufficient.13,14,16

Despite the increasing number of clinical studies and evidence syntheses, the efficacy and safety of PRP therapy compared with standard treatment for DFUs remain subjects of ongoing debate and uncertainty.13,14,16–19 Numerous systematic reviews and meta-analyses have attempted to summarize the available evidence regarding PRP therapy for DFUs.20–30 However, these studies have often yielded inconsistent or heterogeneous findings, with Deng J et al22 reporting that PRP therapy significantly reduces ulcer area (P < 0.01), whereas Syafira F et al24 found no significant difference in ulcer area reduction (P = 0.630). Therefore, these inconsistencies underscore the need for a rigorous and comprehensive appraisal of overlapping meta-analyses to clarify the current evidence base and identify the most credible findings regarding PRP therapy for DFUs.

A cross-sectional appraisal of overlapping meta-analyses provides a robust methodological framework for comparing inconsistent findings across multiple published reviews.31,32 Within medical research, this approach offers several advantages, including the structured identification of discrepancies among meta-analyses, critical assessment of methodological quality, and determination of the most dependable evidence when conclusions are conflicting.31,32 It is particularly applicable to clinical areas in which several meta-analyses have reached discordant conclusions, as it enables comprehensive comparison of methodological robustness, primary study overlap, heterogeneity, and evidentiary strength.33,34 Through this process, cross-sectional analyses can improve the transparency of evidence synthesis and facilitate more informed clinical decision-making. When established evaluation methods, such as the Jadad decision algorithm,35 are incorporated, this approach can help determine which evidence synthesis is the most credible and methodologically rigorous among multiple competing meta-analyses.35 This strategy has been used effectively across a range of medical disciplines.

To date, however, no cross-sectional appraisal of overlapping meta-analyses has specifically examined PRP therapy for DFU. Therefore, the present study was designed to conduct such an evaluation by systematically reviewing and critically assessing the existing evidence, clarifying the efficacy and safety profile of PRP therapy in DFU management, and providing useful implications for clinical decision-making and future research.

Methods

Search Strategy

This study followed the PRISMA 2020 reporting guidelines.36 The study design was guided by relevant previously published methodological studies.31–34 We systematically searched PubMed, Embase, and the Cochrane Library for meta-analyses evaluating PRP therapy vs standard or conventional care for the treatment of DFUs. In the included meta-analyses, standard care and conventional care were considered comparable control interventions, as both referred to routine management of DFUs without PRP therapy. The search period extended from the inception of each database to May 20, 2026. Search terms included combinations of “platelet-rich plasma”, “PRP”, “diabetes”, “diabetic”, “wound”, “ulcer”, “foot”, “meta analysis”, and “systematic review”. To ensure comprehensive retrieval, the reference lists of all included studies were also checked manually for additional eligible publications.

Eligibility Criteria

Eligible studies were required to meet the following criteria: (1) direct comparison of PRP therapy vs standard or conventional care for DFUs; (2) meta-analyses including only randomized controlled trials (RCTs); and (3) reporting of at least one clinically relevant outcome, including complete healing rate, healing time, reduction in ulcer area, infection, amputation, or adverse events. Exclusion criteria: (1) narrative reviews, conference proceedings, letters, case reports and correspondence articles; (2) lacked sufficient information and methodological descriptions; (3) meta-analysis that included non-RCTs; and (4) non-English meta-analysis.

Study Selection

After duplicate records were removed, the retrieved studies were screened in two stages. First, two independent reviewers assessed the titles and abstracts to identify potentially eligible studies based on the predefined inclusion and exclusion criteria. Second, the full texts of potentially relevant articles were reviewed to confirm final eligibility. Discrepancies between the two reviewers were resolved through discussion. When disagreements remained unresolved, a third senior reviewer was involved to reach a final consensus.

Data Extraction

Two reviewers independently extracted data using a standardized extraction form. The collected data included the first author, year of publication, journal, databases searched, last search date, restrictions on language or publication status, number of RCTs included, statistical software, I2 values, and main outcomes relevant to PRP therapy for DFUs, including wound healing, healing time, ulcer area reduction, infection, amputation, and adverse events. Disagreements were resolved through discussion or consultation with a third reviewer.

Quality Appraisal

The methodological quality and evidence strength of the included meta-analyses were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool37,38 and the Oxford Levels of Evidence.39 AMSTAR was applied to evaluate the methodological rigor of each meta-analysis, whereas the Oxford Levels of Evidence were used to classify the overall strength of the evidence. Two reviewers independently performed the assessments according to the predefined criteria. Any discrepancies were resolved through discussion, and unresolved disagreements were adjudicated by a third reviewer.

Jadad Decision Algorithm Application

To clarify discrepancies among the included meta-analyses evaluating PRP therapy for DFUs, the Jadad decision algorithm was used.35 This method assessed possible sources of inconsistency, including differences in inclusion criteria, methodological quality, statistical analysis, outcome definitions, and clinical question framing. Three reviewers independently applied the algorithm to determine which meta-analysis offered the most robust and clinically relevant evidence.

Results

Study Screening

Figure 1 presents the study selection process. A total of 192 records were retrieved through the initial search, and eleven meta-analyses were finally included after screening according to the predefined eligibility criteria.20–30 Table 1 summarizes the basic features of these studies. The included meta-analyses were published between 2018 and 2025, with their primary RCTs conducted from 1992 to 2024. The number of RCTs included in each meta-analysis varied from 8 to 22 (Table 2).

Figure 1.

A flowchart of study selection process for records identified and screened, leading to 11 included studies. A flowchart detailing the study selection process. It begins with records identified through Pubmed database searching, totaling 55 and additional records identified through other sources, totaling 137. These lead to 73 records after duplicates are removed. From these, 42 are excluded by title and abstract, leaving 31 records screened by full text. Of these, 20 are excluded with reasons: 11 for not mentioning PRP treatment, 5 for not being meta-analysis or systematic review and 4 for including non-RCTs. Finally, 11 records are included in this study.

PRISMA 2020 flow chart of study selection for meta-analyses comparing platelet-rich plasma vs standard care for diabetic foot ulcers. A total of 192 records were identified, of which 11 meta-analyses met the eligibility criteria after screening.

Table 1.

Characteristics of Included Meta-Analyses

First Author Publication Year Journal Last Literature Search Date Number of Included RCTs
Hu Z20 2019 Advances in Wound Care July, 2019 8
Li Y29 2019 Journal of Diabetes May, 2019 15
Ding H28 2019 Advances in Wound Care May, 2019 15
Dai J21 2020 Journal of Diabetes And Its Complications August, 2020 10
Deng J22 2023 Journal of Orthopaedic Surgery And Research May, 2023 22
Su Y23 2023 Journal of Wound Care December, 2023 17
Syafira F24 2023 Diabetes Epidemiology and Management August, 2023 9
Platini H30 2024 Therapeutics And Clinical Risk Management January, 2024 8
Ruiz-Muñoz M26 2024 Journal of Diabetes And Its Complications February, 2024 11
Peng Y25 2024 Annals of Vascular Surgery January, 2024 10
Xu H27 2025 Acta Diabetologica October, 2025 15

Table 2.

Primary Studies Included in Meta-Analyses

First Author (Year) Hu Z
(2019)20
Li Y
(2019)29
Ding H (2019)28 Dai J
(2020)21
Deng J (2023)22 Su Y (2023)23 Syafira F
(2023)24
Platini H (2024)30 Ruiz-Muñoz M (2024)26 Peng Y (2024)25 Xu H (2025)27
Steed DL (1992)40 + +
Holloway
(1993)41
+
Steed DL (1996)42 + +
Saldalamacchia G (2004)43 + + + + + + + +
Driver VR (2006)16 + + + + + + + +
Kakagia DD (2007)44 + + +
Friese G (2007)45 + + + +
Wei C (2008)46 +
Chen H (2008)47 + +
Yan H (2008)48 +
Wang Y (2009)49 +
Jeong SH (2010)50 +
Saad Setta H (2011)51 + + + + +
Zhu S (2012)52 +
Li L (2012)53 +
Serra R (2013)54 + + +
Qi K (2014)55 + +
Ma L (2014)56 + +
Zhou X (2015)57 + +
Li L (2015)17 + + + + + + + + + +
Liu G (2016)58 + +
Kontopodis N (2016)59 +
Zhang L (2016)60 + +
Karimi R (2016)61 + + + +
Ahmed M (2017)62 + + + + + + + + + +
Yang L (2017)63 + +
Miłek T (2017)64 +
Goda A (2018)65 + + +
Game F (2018)66 +
Abd El-Mabood (2018)67 + +
Singh SP (2018)68 + + + + +
Qin X
(2019)69
+
Gude W (2019)70 + + +
Rainys D (2019)71 + + +
Elsaid A (2020)18 + + + + + + +
Xie J (2020)72 + +
He M (2020)73 +
Smith OJ (2020)74 + +
Habeeb T (2020)75 + + +
Liao X (2020)76 + + +
Gupta A (2021)77 +
Alamdari NM (2021)78 + + + + + +
Meamar R (2021)79 +
Helmy Y (2021)80 + +
Rajendran S (2021)81 +
Mohammadi Tofigh A (2022)82 +
Ullah A (2022)83 + +
Orban YA (2022)84 +
Hossam EM (2022)85 + + +
Huang J (2023)86 +
Essa MS (2023)87 +
Sheng X (2024)88 +

Notes: (+): The corresponding primary study was encompassed by that meta‑analysis.

Search Methodology

Of the eleven included meta-analyses on PRP therapy for DFUs, four searched only English-language literature20,24,26,30 while seven either applied no language restriction or did not clearly report this information.21–23,25,27–29 PubMed and the Cochrane Library were the most commonly searched databases, whereas MEDLINE, Web of Science, Embase, Google Scholar, and Scopus were used inconsistently among studies. Table 3 presents a detailed overview of the search methods.

Table 3.

Search Methodology for Included Meta-Analyses

First Author (Year) Language Restriction Publication Status Restriction Search Database
PubMed Medline Embase Cochrane Library CINAHL Web of Science Google Scholar Others
Hu Z (2019)20 Yes Yes + + + +
Li Y (2019)29 No NA + + + +
Ding H (2019)28 No NA + +
Dai J (2020)21 No NA + + + + +
Deng J (2023)22 No Yes + + + +
Su YN (2023)23 No NA + + + + +
Syafira F (2023)24 Yes Yes + + +
Platini H (2024)30 Yes NA + + + +
Ruiz-Muñoz M (2024)26 Yes Yes + + +
Peng Y (2024)25 NA NA + + +
Xu H (2025)27 No Yes + + +

Notes: (+): Respective database was searched by that meta-analysis.

Methodological Quality

All included meta-analyses evaluating PRP therapy for DFUs synthesized evidence derived exclusively from RCTs, corresponding to Level II evidence according to the Oxford criteria (Table 4). RevMan was the most frequently used statistical software across the included studies,21,23,25,26,29 and two meta-analyses reported using the GRADE approach to assess the certainty of evidence22,29 (Table 4). The methodological quality of the included reviews, assessed using AMSTAR, showed scores ranging from 6 to 10, with a median score of 8 (Table 5).

Table 4.

Methodological Information of Included Meta-Analyses

First Author (Year) Study Design Level of Evidence Software Used GRADE Use Subgroup Analysis Sensitivity Analysis
Hu Z (2019)20 RCT Level II Stata No Yes Yes
Li Y (2019)29 RCT Level II RevMan Yes Yes NA
Ding H (2019)28 RCT Level II Stata NA Yes Yes
Dai J (2020)21 RCT Level II RevMan, Stata No NA Yes
Deng J (2023)22 RCT Level II Stata Yes Yes Yes
Su YN (2023)23 RCT Level II RevMan No Yes Yes
Syafira F (2023)24 RCT Level II MedCalc No NA NA
Platini H (2024)30 RCT Level II RevMan No Yes Yes
Ruiz-Muñoz M (2024)26 RCT Level II RevMan, SPSS No NA Yes
Peng Y (2024)25 RCT Level II RevMan No NA Yes
Xu H (2025)27 RCT Level II R No Yes Yes

Notes: RCT, randomized clinical trial.

Table 5.

AMSTAR Scores for the Included Studies

Items Hu Z (2019)20 Li Y (2019)29 Ding H (2019)28 Dai J (2020)21 Deng J (2023)22 Su YN (2023)23 Syafira F (2023)24 Platini H (2024)30 Ruiz-Muñoz M (2024)26 Peng Y (2024)25 Xu H (2025)27
1. Was an a priori design provided? 0 0 0 0 0 1 0 0 1 0 0
2. Was there duplicate study selection and data extraction? 1 1 1 1 1 1 0 0 1 0 1
3. Was a comprehensive literature search performed? 1 1 1 1 1 1 1 1 1 1 1
4. Was the status of publication (ie grey literature) used as an inclusion criterion?-unpublished, ongoing 1 0 0 0 0 0 0 0 0 0 0
5. Was a list of studies (included and excluded) provided? 1 1 1 1 1 1 1 1 1 1 1
6. Were the characteristics of the included studies provided? 1 1 1 1 1 1 1 1 1 1 1
7. Was the scientific quality of the included studies assessed and documented? 1 1 1 1 1 1 1 1 1 1 1
8. Was the scientific quality of the included studies used appropriately in formulating conclusions? 1 1 1 1 0 1 0 0 0 0 1
9. Were the methods used to combine the findings of studies appropriate? 1 0 1 1 1 1 0 1 1 1 1
10. Was the likelihood of publication bias assessed? 1 1 1 1 1 1 1 1 1 0 1
11. Was the conflict of interest stated? 1 1 1 1 1 1 1 1 1 1 1
Total scores 10 8 9 9 8 10 6 7 9 6 9

Evaluation of Heterogeneity

Statistical heterogeneity across the included meta-analyses of PRP therapy for DFUs was assessed using the I2 statistic (Table 6). Several outcomes showed substantial between-study heterogeneity, as indicated by I2 values greater than 75%. Potential sources of this heterogeneity include differences in participant characteristics, PRP treatment regimens, and follow-up durations among the primary trials. Sensitivity analyses were reported in nine studies,20–23,25–28 whereas two meta-analyses did not report sensitivity analyses. In addition, four meta-analyses did not clearly state whether subgroup analyses had been conducted21,24–26 (Table 4).

Table 6.

I2 Statistic Values for Each Variable in Meta-Analyses

Items Hu Z (2019)20 Li Y (2019)29 Ding H (2019)28 Dai J (2020)21 Deng J (2023)22 Su YN (2023)23 Syafira F (2023)24 Platini H (2024)30 Ruiz-Muñoz M (2024)26 Peng Y (2024)25 Xu H (2025)27
Healing proportion 42.2% 12% 0% 57% 54.8% 0% 79.4% 23% 0% 73% 29%
Healing time 0% 67% 51.5% 78% 97.5% 95.7% 96% 100% 94%
Ulcer area reduction 0% 36% 98.2%
Ulcer complications 0% 53% 0% 19%
Granulation tissue formation NA
Adverse events NA 0% 0% 34.9% 0% NA
Recurrences 66.3%
Amputation rate 0% 0% 0% 41%
Length hospital stay NA 90%
Ulcer healing velocity 65.1%
Death rate 0%
Treatment Cost NA

Results of Jadad Decision Algorithm

To determine the most reliable body of evidence among the included meta-analyses evaluating PRP therapy for DFUs, the Jadad decision algorithm was applied.35 The comparative assessment process is summarized in Figure 2. Although all meta-analyses addressed a broadly similar clinical question, their conclusions varied because of differences in eligibility criteria, included RCTs, methodological quality assessment, language restrictions, and statistical approaches. According to the Jadad framework, the selection of the best available evidence should consider several factors, including the methodological quality of the included trials, publication status, language limitations, comprehensiveness of the search strategy, and whether individual patient data were used. Based on these criteria, the meta-analysis by Su YN et al23 was considered the most rigorous and clinically informative synthesis (Figure 3). This study found that autologous PRP was associated with a higher complete ulcer healing rate than standard care, with low statistical heterogeneity. PRP also shortened the time to complete healing, while no significant difference was observed in overall adverse events between the PRP and control groups.

Figure 2.

A heatmap of PRP for DFUs outcomes by meta-analyses, with legend categories and no cell numbers. Heatmap titled, Outcomes. Columns list 11 meta analyses: Hu Z 2019; Li Y 2019; Ding H 2019; Dai J 2020; Deng J 2023; Su YN 2023; Syafira F 2023; Platini H 2024; Ruiz Munoz M 2024; Peng Y 2024; Xin H 2025. Rows list 12 outcomes: Healing proportion; Healing time; Ulcer area reduction; Ulcer complications; Granulation tissue formation; Adverse events; Recurrences; Amputation rate; Length hospital stay; Ulcer healing velocity; Death rate; Treatment Cost. Legend categories: Favoring PRP therapy; Favoring standard care; No difference; Not reporting. Cells contain no numbers. Cell categories by row. Healing proportion: Favoring PRP therapy in all 11 columns. Healing time: No difference in Hu Z 2019; Favoring PRP therapy in Li Y 2019, Ding H 2019, Dai J 2020, Deng J 2023, Su YN 2023, Syafira F 2023, Platini H 2024, Peng Y 2024, Xin H 2025; Not reporting in Ruiz Munoz M 2024. Ulcer area reduction: Favoring PRP therapy in Hu Z 2019 and Deng J 2023; No difference in Syafira F 2023; Not reporting in Li Y 2019, Ding H 2019, Dai J 2020, Su YN 2023, Platini H 2024, Ruiz Munoz M 2024, Peng Y 2024, Xin H 2025. Ulcer complications: No difference in Hu Z 2019; Favoring PRP therapy in Dai J 2020 and Xin H 2025; Not reporting in Li Y 2019, Ding H 2019, Deng J 2023, Su YN 2023, Syafira F 2023, Platini H 2024, Ruiz Munoz M 2024, Peng Y 2024. Granulation tissue formation: Favoring PRP therapy in Syafira F 2023; Not reporting in the other 10 columns. Adverse events: Favoring PRP therapy in Li Y 2019, Ding H 2019, Dai J 2020, Syafira F 2023, Peng Y 2024; No difference in Deng J 2023, Su YN 2023, Xin H 2025; Not reporting in Hu Z 2019, Platini H 2024, Ruiz Munoz M 2024. Recurrences: No difference in Hu Z 2019; Favoring PRP therapy in Syafira F 2023; Not reporting in the other 9 columns. Amputation rate: No difference in Hu Z 2019 and Syafira F 2023; Favoring PRP therapy in Deng J 2023, Platini H 2024, Xin H 2025; Not reporting in Li Y 2019, Ding H 2019, Dai J 2020, Su YN 2023, Ruiz Munoz M 2024, Peng Y 2024. Length hospital stay: Favoring PRP therapy in Li Y 2019 and Platini H 2024; Not reporting in the other 9 columns. Ulcer healing velocity: No difference in Hu Z 2019; Not reporting in the other 10 columns. Death rate: No difference in Hu Z 2019; Not reporting in the other 10 columns. Treatment Cost: Favoring PRP therapy in Li Y 2019; Not reporting in the other 10 columns.

Outcome reporting matrix of the 11 included meta-analyses on PRP for DFUs. Rows show 12 outcome measures, columns show individual meta-analyses. Color intensity indicates the direction and significance of pooled effect estimates (Blue: favoring PRP therapy; Green: favoring standard care; Yellow: no difference; Gray: not reported).

Figure 3.

A flowchart depicting the Jadad decision algorithm for resolving discordant meta-analysis findings. The flowchart illustrates the Jadad decision algorithm applied to resolve discordant findings among meta-analyses. It begins with selecting the question closest to the problem to be solved. If the same question is identified, eligibility criteria are checked. If the same trials are used, the process checks for the same quality. If yes, it leads to assessing and comparing data extraction, heterogeneity testing and data synthesis. If no, the study with the highest quality is selected. If trials differ, selection criteria are assessed. If the same, search strategies and application of selection criteria are compared. If not, publication status, methodological quality, language restrictions and individual patient data analysis are assessed. The selected meta-analysis by Su YN et al (2023) is identified as the most rigorous source.

Jadad decision algorithm flow chart applied to resolve discordant findings among the included meta-analyses. The algorithm systematically evaluates differences in publication status, methodological quality, language restrictions, and statistical approaches to identify the most credible evidence synthesis. Following this framework, the meta-analysis by Su YN et al (2023) was selected as the most rigorous and clinically informative source.

Discussion

DFUs represent a major global public health burden due to their high prevalence, chronicity, and substantial economic costs.1,2 These challenges underscore the need for effective, evidence-based, and cost-efficient therapeutic strategies.3–5 PRP has emerged as an adjunctive treatment option in the management of DFUs, alongside standard wound care approaches.12–14 However, existing meta-analyses have reported inconsistent findings regarding its clinical efficacy and safety.22,24 Cross-sectional analyses of overlapping meta-analyses offer a structured approach to synthesizing and comparing existing evidence by evaluating the methodological quality, consistency, and heterogeneity across systematic reviews.31,33 This method helps identify the most reliable evidence and reconcile discrepancies among published studies.32,34 To our knowledge, this study represents the first cross-sectional analysis of overlapping meta-analyses specifically focusing on PRP therapy for DFUs. By comprehensively assessing methodological quality, heterogeneity, and consistency of findings across multiple meta-analyses, we aimed to clarify the overall evidence regarding the effectiveness of PRP in this clinical context.

Although the included meta-analyses evaluating PRP therapy for DFUs were conducted within overlapping time periods and generally applied similar search strategies, substantial heterogeneity was observed in the selection of primary studies as well as in the reported conclusions.20–30 These inconsistencies reflect the inherent challenges in synthesizing evidence when systematic reviews differ in methodological design, analytical approaches, and interpretation of findings. As previously emphasized by Jadad et al,35 such discrepancies may arise from variations in clinical question framing, eligibility criteria, data extraction procedures, risk-of-bias assessment tools, evaluation of study combinability, and statistical synthesis methods. To address these limitations, the present study applied the Jadad decision algorithm to identify the most methodologically robust evidence among conflicting reviews.35 This structured framework prioritizes transparency, methodological rigor, and consistency in decision-making, thereby enabling a systematic resolution of overlapping and potentially discordant meta-analytic findings.35

Based on this approach, the meta-analysis by Su YN et al23 was identified as the highest-quality evidence source. This study suggested that autologous PRP, as an adjunct to standard care, improves complete ulcer healing and shorten the time to complete healing in patients with DFUs, with no statistically significant increase in reported adverse events.23 Nevertheless, the observed benefits were primarily reflected in wound-healing outcomes, whereas complication-related endpoints, including wound-related infection, amputation, and serious adverse events, did not show statistically significant differences between groups.23 These findings should be interpreted with caution because the included trials varied in ulcer characteristics, PRP preparation and application methods, treatment duration, and follow-up periods, which may partly account for the inconsistency across secondary outcomes.23 Overall, PRP appears to offer a potential therapeutic advantage in selected patients, but its efficacy may vary depending on clinical context and implementation details. Therefore, PRP may be considered a promising adjunctive therapy for DFUs, while further high-quality RCTs are required to confirm its effectiveness across standardized clinical settings.

Another important finding of this study is the overall methodological quality of the included meta-analyses evaluating PRP therapy for DFUs. All the synthesized evidence was derived exclusively from RCTs, which are generally considered to provide a high level of clinical evidence. However, notable variation in AMSTAR scores suggests differences in the methodological rigor of the included systematic reviews, highlighting the necessity of critically appraising review quality rather than relying solely on pooled results.37,38 In several studies, sensitivity analyses further demonstrated that methodological choices may influence the stability of findings, underscoring the importance of robust analytical approaches. In this context, the application of the Jadad decision algorithm35 enabled the identification of the most reliable evidence by integrating considerations of publication characteristics, methodological quality, and analytical consistency, thereby supporting a more dependable overall conclusion.

Our findings have important implications for both clinical practice and future research regarding PRP therapy for DFUs. From a clinical perspective, the results indicate that PRP should not be regarded as universally superior or applied indiscriminately across all patients. Instead, treatment decisions should be individualized based on ulcer characteristics, patient conditions, and resource availability. In routine practice, PRP may be considered as an adjunctive option within a comprehensive wound care strategy, but its use should take into account local resources, preparation protocols, costs, and clinical expertise. At the same time, its potential benefits may be more pronounced in selected patients with complex or refractory ulcers, where enhanced biological activity may contribute to improved wound healing outcomes. From a research perspective, the present analysis highlights the need for more standardized and methodologically rigorous evidence synthesis in this field. Future meta-analyses should adopt comprehensive search strategies, clearly defined eligibility criteria, and transparent approaches to heterogeneity assessment. In addition, well-designed, large-scale RCTs with longer follow-up periods are still required to further clarify the comparative effectiveness and safety of PRP across different patient populations and ulcer subtypes.

This study has several limitations that should be acknowledged. First, although searches were conducted in three major biomedical databases, the restriction to English-language publications may have introduced language bias and resulted in the omission of relevant evidence from non-English publications. Second, because this study evaluated published meta-analyses rather than individual RCTs, the findings may be affected by overlap among primary trials and by the reporting quality of the included reviews. Third, although inclusion was limited to meta-analyses derived exclusively from RCTs to strengthen evidence quality, the resulting body of evidence was still categorized as Level II according to the Oxford system. As a result, the current study is unable to provide conclusions supported by Level I evidence, which represents the highest level of clinical certainty. Therefore, further well-designed, large-scale RCTs with standardized treatment protocols and longer follow-up periods are required to confirm the clinical efficacy and safety of PRP.

Conclusion

This cross-sectional appraisal of overlapping meta-analyses indicates that PRP is an effective adjunctive therapy for DFUs, significantly improving complete healing rates and shortening healing time without a statistically significant increase in adverse events. The prevailing uncertainty in the evidence base relates not to whether PRP confers benefit, but rather to the magnitude of effect and optimal preparation protocols. Clinically, PRP may be considered for selected patients with refractory ulcers, while future large-scale, standardized randomized controlled trials are warranted to establish definitive guidance on dosing, application methods, and long-term safety.

Funding Statement

Clinical Research Center for Metabolic Diseases (Integrated Traditional Chinese and Western Medicine) of Chongqing (No. SQMS2026DXB-001), National Natural Science Foundation of China (82205089), Fundamental Research Funds for the Central Public Welfare Research Institutes (ZZ13-YQ-030), Clinical Research Center Construction Project of Guang’anmen Hospital, CACMS (2022LYJSZX13), High Level Chinese Medical Hospital Promotion Project (HLCMHPP2023009), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2025ZD0550900).

Abbreviations

DFUs, Diabetic Foot Ulcers; PRP, platelet-rich plasma; RCTs, Randomized Controlled Trials; AMSTAR, Assessment of Multiple Systematic Reviews.

Data Sharing Statement

Data are available on reasonable request to the corresponding author (Tianlin Wen).

Author Contributions

Ying Du: Data curation, methodology, investigation, validation, formal analysis, writing—original draft;

Xinxin Meng, Bolun Zhang and Qiantai Gao: Methodology, investigation, visualization, formal analysis, writing—review and editing;

Zhiwei Jia, Tianlin Wen and Xiyan Zhao: Conceptualization, supervision, writing—review and editing.

All authors took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors declare no conflicts of interest in this work.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data are available on reasonable request to the corresponding author (Tianlin Wen).


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