Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Jul;62(7):1081-1095.
doi: 10.1007/s00592-024-02426-7. Epub 2024 Dec 26.

Effectiveness of most common adjuvant wound treatments (skin substitutes, negative pressure wound therapy, hyperbaric oxygen therapy, platelet-rich plasma/fibrin, and growth factors) for the management of hard-to-heal diabetic foot ulcers: a meta-analysis of randomized controlled trials for the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome

Matteo Monami  1 , Alessia Scatena  2   3   4 , Benedetta Ragghianti  5   3   4 , Cesare Miranda  6   3   4 , Luca Monge  7   3   4 , Antonio Silverii  5   3   4 , Luigi Uccioli  8   3   4 , Cristiana Vermigli  3   4   9 ; Panel of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome; SID and AMD
Collaborators, Affiliations
Meta-Analysis

Effectiveness of most common adjuvant wound treatments (skin substitutes, negative pressure wound therapy, hyperbaric oxygen therapy, platelet-rich plasma/fibrin, and growth factors) for the management of hard-to-heal diabetic foot ulcers: a meta-analysis of randomized controlled trials for the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome

Matteo Monami et al. Acta Diabetol. 2025 Jul.

Abstract

Aim: To assess the effects of several adjuvant therapies (AT) commonly used in the treatment of diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome.

Methods: A Medline and Embase search were performed up to May 20th, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with DFU comparing AT with placebo/standard of care (SoC), with a duration of at least 12 weeks. Prespecified endpoints were: ulcer healing (principal), time-to-healing, major and minor amputation, serious adverse events (SAE), and all-cause mortality. AT assessed were: growth factors (GF), Platelet-rich plasma and fibrin (PRP/F), skin substitutes (SS), negative pressure wound therapy (NPWT), and hyperbaric oxygen therapy (HBOT). Mantel-Haenzel Odds ratios and 95% confidence intervals (MH-OR, 95% CIs) were either calculated or extracted directly from the publications. Weighted mean differences and 95% CIs were calculated for continuous variables.

Results: Fifty-one studies fulfilled all inclusion criteria (3, 5, 27, 8, and 8 with GF, PRP/F, SS, NPWT, and HBOT, respectively). Participants treated with any of the explored AT had a significantly higher ulcer healing rate (MH-OR ranging from 2.17 to 4.18) and shorter time-to-healing in comparison with SoC/placebo. Only PRP/F and HBOT showed a significantly lower risk of major amputation (MH-OR: 0.32(0.11;0,93; p = 0.04 and 0.28(0.10;0,79; p = 0.02, respectively), despite a higher risk of SAE. No other significant effects on the above-reported prespecified endpoints were observed. For the primary endpoint, the quality of evidence was rated as "high" for all the AT, except for NPWT ("moderate").

Conclusions: In conclusion, AT can actively promote wound healing and shorten time-to-healing in patients with DFU. HBOT and PRP/F also showed a reduction of the risk of major amputation, despite a higher rate of SAE.

Keywords: Adjuvant therapy; Diabetic foot ulcers; Guidelines; Healing; Meta-analysis.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflicts of interest: The other authors do not have any direct relevant conflicts of interest to disclose.

References

    1. Aronson R, Chu L, Joseph N, Brown R (2021) Prevalence and risk evaluation of diabetic complications of the foot among adults with type 1 and type 2 diabetes in a large Canadian population (PEDAL Study). Can J Diabetes 45(7):588–593. https://doi.org/10.1016/j.jcjd.2020.11.011 - DOI - PubMed
    1. Morbach S, Furchert H, Gröblinghoff U, Hoffmeier H, Kersten K, Klauke GT et al (2012) Long-term prognosis of diabetic foot patients and their limbs: amputation and death over the course of a decade. Diabetes Care 35(10):2021–2027. https://doi.org/10.2337/dc12-0200 - DOI - PubMed - PMC
    1. Elgzyri T, Larsson J, Nyberg P, Thörne J, Eriksson KF, Apelqvist J (2014) Early revascularization after admittance to a diabetic foot center affects the healing probability of ischemic foot ulcer in patients with diabetes. Eur J Vasc Endovasc Surg 48(4):440–446. https://doi.org/10.1016/j.ejvs.2014.06.041 - DOI - PubMed
    1. Tan JS, Friedman NM, Hazelton-Miller C, Flanagan JP, File TM Jr (1996) Can aggressive treatment of diabetic foot infections reduce the need for above-ankle amputation? Clin Infect Dis 23(2):286–291. https://doi.org/10.1093/clinids/23.2.286 - DOI - PubMed
    1. Meloni M, Giurato L, Monge L, Miranda C, Scatena A, Ragghianti B et al (2024) Effect of a multidisciplinary team approach in patients with diabetic foot ulcers on major adverse limb events (MALEs): systematic review and meta-analysis for the development of the Italian guidelines for the treatment of diabetic foot syndrome. Acta Diabetol. https://doi.org/10.1007/s00592-024-02246-9 - DOI - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources