Effective treatments for non-healing diabetic ulcers

Diabetic foot ulcer

Non-healing leg ulcers are a major burden for people with diabetes and for the health service.  This evidence review by the US Department of Veterans’ Affairs focuses on treatments approved by the US Food and Drug Administration but contains important findings that could be applicable in any setting.

Clinical question

The review addresses the following three questions in relation to diabetes ulcers:

  • What are the efficacy and harms of therapies for diabetic ulcers?
  • Is efficacy dependent on ancillary therapies?
  • Does efficacy differ according to patient demographics, comorbid conditions, treatment compliance, or activity level?

The review is available free as a full text PubMed e-book.


The reviewers conducted a literature search and found 35 trials of treatments of diabetic leg ulcers.  These trials looked at:

  • collagen (4 trials, n=489)
  • biological dressings (2 trials, n=124
  • biological skin equivalents (7 trials, n=989)
  • platelet-derived growth factors (9 trials, n=990)
  • platelet-rich plasma (2 trials, n=96)
  • silver products (4 trials, n=280)
  • negative pressure wound therapy (3 trials, n=418)
  • hyperbaric oxygen therapy (5 trials, n=326)
  • ozone-oxygen therapy (1 trial, n=61).

The studies were evaluated for methodological quality.


The reviewers found that there was conflicting evidence from the studies, many of which were of low quality and short duration.

However, based on the available findings we conclude that for patients with diabetic chronic ulcers, there is moderate strength of evidence that the biological skin equivalent Apligraf and negative pressure wound therapy improve healing compared to standard care.

There was weak evidence to support the use of collagen, the biological skin equivalent Dermagraft, platelet-derived growth factors, silver cream, and hyperbaric oxygen therapy.

The reviewers report that heterogeneity was a significant problem and limited their ability to answer the questions they had set themselves.  Further large, well-conducted studies are needed to investigate these questions, with longer duration and direct comparisons between competing treatments.


  • Some of the treatment modalities may not be applicable outside of a US setting.
  • They did only included MEDLINE and the Cochrane Library in their search;  there may be other studies that they didn’t find.
  • It’s not clear whether the studies were evaluated by blind, independent reviewers.


Greer N, Foman N, Dorrian J, Fitzgerald P, MacDonald R, Rutks I, Wilt T. (eds) Advanced Wound Care Therapies for Non-Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review. Washington (DC): Department of Veterans Affairs; 2012 Nov. VA Evidence-based Synthesis Program Reports.

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I am an information scientist with an interest in making knowledge from systematic research more accessible to people who need it. This means you. I've been attempting this in the area of Evidence-Based Health Care since 1995. So far the results have been mixed. For some reason we expected busy clinicians to search databases and appraise papers instead of seeing patients. We also expected publishers to make the research freely available to the people who paid for it.. Ha! Hence The National Elf service.

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