Diabetic Foot Ulcer: An Evidence-based Treatment Update

Liza R. Braun; Whitney A. Fisk; Hadar Lev-Tov; Robert S. Kirsner; Roslyn R. Isseroff


Am J Clin Dermatol. 2014;15(3):267-281. 

In This Article

Abstract and Introduction


Background. Diabetic foot ulcers (DFUs) are extremely debilitating and difficult to treat. Multidisciplinary management, patient education, glucose control, debridement, offloading, infection control, and adequate perfusion are the mainstays of standard care endorsed by most practice guidelines. Adjunctive therapies represent new treatment modalities endorsed in recent years, though many lack significant high-powered studies to support their use as standard of care.

Objective. This update intends to identify recent, exclusively high level, evidence-based evaluations of DFU therapies. Furthermore, it suggests a direction for future research.

Methods PubMed, Embase, Ovid Technologies, CINAHL, Cochrane, and Web of Science databases were systematically searched for recent systematic reviews published after 2004, and randomized controlled trials published in 2012–2013 that evaluated treatment modalities for DFUs. These papers are reviewed and the quality of available evidence is discussed.

Results A total of 34 studies met inclusion criteria. Studied therapies include debridement, off-loading, negative pressure therapy, dressings, topical therapies, hyperbaric oxygen therapy, growth factors, bioengineered skin substitutes, electrophysical therapy, and alternative therapy. Good-quality evidence is lacking to justify the use of many of these therapies, with the exception of standard care (offloading, debridement) and possibly negative pressure wound therapy.

Limitations. There is an overall lack of high-level evidence in new adjunctive management of DFU. Comparison of different treatment modalities is difficult, since existing studies are not standardized.

Conclusions. Many therapeutic modalities are available to treat DFU. Quality high-level evidence exists for standard care such as off-loading. Evidence for adjunctive therapies such as negative pressure wound therapy, skin substitutes, and platelet-derived growth factor can help guide adjunctive care but limitations exist in terms of evidence quality.

1 Introduction

In the USA, diabetes mellitus (DM) afflicts 9.9% of the population over 40 years of age, of which 30% suffer from lower extremity disease.[1] Development of a diabetic foot ulcer (DFU) is associated with staggeringly high mortality rates of 16.7% at 12 months and 50% at 5 years—rates comparable to mortality rates of colon cancer.[2] Furthermore, patients with DM and new-onset DFU have significantly reduced survival rates compared with age- and sex-matched controls with DM but without DFUs (72 and 86% 3-year survival, respectively).[3] In the USA, healthcare costs are estimated to be 5.4 times higher in the first year after a diagnosis of DFU than for patients with DM without an ulcer.[2,3] Therefore, management and intervention of patients with DM and DFU must be adequately addressed before onset of severe complications. Unfortunately, DM is associated with a 15–25% lifetime risk for developing DFU,[2] and once ulceration occurs, healing is difficult and lower extremity amputations (LEAs) common. Nearly 90% of patients undergoing LEA have a history of a DFU, and LEAs are associated with a doubling in the risk of death. In 2008, more than 15,000 LEAs were performed on Medicare beneficiaries with DM, with the annual incidence of LEA in Medicare beneficiaries with DM estimated at 5 per 1,000 in 2006 and 2007, and 4 per 1,000 in 2008. The cost to treat those who have had LEA is excessive, with an average $US52,000 reimbursed annually for a Medicare beneficiary with DM and a LEA from 2006–2008.[4–18]

Fortunately, there are growing efforts towards international consensus on management and rapid communication on enhancing standard of care and reviewing novel therapies. These therapies address various mechanisms of DFU formation in order to achieve wound healing. DFU standard of care is critical; however, for those not responding to standard care, new adjunctive modalities may provide opportunities for healing. Yet, while treatment options have expanded in recent years, the cost effectiveness and efficacy of these modalities remain in question.

This review intends to identify recent evidence-based evaluations of all DFU therapies, focusing exclusively on high-level evidence. Furthermore, it identifies gaps in current data and suggests direction for further investigation.