Challenges in Treating Diabetic Foot Ulcers
The fundamental challenge in treating diabetic foot ulcers is that even with optimal standard care—including offloading, debridement, infection control, and revascularization—many ulcers fail to heal, yet most adjunctive therapies lack strong evidence to justify their routine use. 1
Core Treatment Barriers
Limited Evidence for Advanced Therapies
Most adjunctive therapies are not recommended for routine use despite being widely marketed, as the 2024 IWGDF guidelines provide strong recommendations against using cellular skin substitutes, acellular skin substitutes, growth factors, physical therapies, and most pharmacological agents due to low-quality evidence 1
The effectiveness of many novel treatments remains uncertain due to small randomized controlled trials with high risk of bias, making it difficult to assess true clinical benefit 2, 3, 4
Even becaplermin (platelet-derived growth factor), the only FDA-approved topical growth factor, showed modest benefit (50% healing vs 35% placebo at 20 weeks) but carries a boxed warning for potential cancer risk, limiting its use 5
Standard of Care Compliance Difficulties
Adequate offloading remains the cornerstone of treatment but is frequently inadequate in practice, with non-removable knee-high devices (total contact casts) being most effective but underutilized due to resource limitations, patient compliance issues, and provider inexperience 1, 6
Sharp debridement must be performed repeatedly based on clinical need, requiring frequent clinic visits and skilled practitioners, which creates access barriers for many patients 1, 6
Maintaining a strict non-weight-bearing regimen is essential but extremely difficult for patients to adhere to in real-world settings, particularly those with limited mobility aids or social support 1
Vascular Assessment and Intervention Challenges
Identifying critical ischemia requiring urgent revascularization (ankle pressure <50 mmHg or ABI <0.5) is straightforward, but the decision becomes complex when perfusion is borderline (toe pressure <30 mmHg or TcpO2 <25 mmHg) 1, 7
Even when revascularization is indicated, not all patients are candidates due to anatomical limitations, lack of autogenous vein, or significant comorbidities, and local expertise in both endovascular and surgical techniques varies widely 1
Pharmacological treatments to improve perfusion have not been proven beneficial, leaving revascularization as the only option for ischemic ulcers 1
Infection Management Complexity
Distinguishing between superficial infection requiring oral antibiotics and deep infection requiring urgent surgical intervention and parenteral antibiotics can be challenging, particularly when systemic signs are absent 1, 7
Empiric antibiotic selection must balance coverage of common pathogens (S. aureus, streptococci, gram-negatives, anaerobes) against the risk of resistance, and obtaining appropriate wound cultures from debrided tissue (not swabs) requires proper technique 1
Osteomyelitis diagnosis remains difficult, often requiring bone biopsy for definitive diagnosis, and treatment duration is prolonged (typically 6 weeks or longer) 1
Limited Adjunctive Options for Non-Healing Ulcers
Few Conditionally Recommended Therapies
Only three adjunctive therapies received conditional recommendations in the 2024 IWGDF guidelines: sucrose-octasulfate impregnated dressing (moderate certainty), autologous leucocyte-platelet-fibrin patch (moderate certainty), and hyperbaric oxygen therapy (low certainty)—all requiring that standard care has already failed 1, 6
Negative pressure wound therapy is recommended only for post-surgical wounds, with a strong recommendation against its use for non-surgical diabetic foot ulcers 1
Placental-derived products received only conditional recommendation with low certainty evidence, making their routine use difficult to justify 1
Resource and Expertise Limitations
Hyperbaric oxygen therapy requires specialized facilities and multiple treatment sessions (typically 30-40 sessions), making it accessible only where resources already exist and cost-effectiveness remains unestablished 1
Autologous leucocyte-platelet-fibrin patch requires regular venepuncture and specialized preparation, limiting its availability to centers with appropriate expertise 1, 6
The 2024 guidelines explicitly recommend against topical oxygen, other gases (cold atmospheric plasma, ozone, nitric oxide, CO2), and all physical therapies despite their availability in some centers 1
Prognostic and Monitoring Challenges
High Failure and Mortality Rates
Mortality rates associated with diabetic foot ulcers are estimated at 5% in the first 12 months and 42% at 5 years, reflecting the severity of underlying disease and complications 2
Treatment should be adjusted if insufficient improvement (approximately 30% reduction in ulcer area) is not observed after 2 weeks, but determining which alternative therapy to use remains unclear given limited evidence 6, 5
Even after healing, recurrence risk remains high without appropriate therapeutic footwear with demonstrated plantar pressure-relieving effect 6
Lack of Standardization
Comparison of different treatment modalities is difficult since existing studies are not standardized in terms of patient selection, ulcer characteristics, standard care protocols, and outcomes measured 3, 4
The Wagner and University of Texas classification systems help guide prognosis, but treatment algorithms based on these classifications lack strong evidence for many interventions 8
Common Pitfalls in Clinical Practice
Failing to provide adequate offloading is the most common pitfall, with providers often relying on removable devices that patients do not consistently use rather than non-removable options 6
Overreliance on advanced therapies before optimizing standard care (debridement, offloading, infection control, vascular assessment) wastes resources and delays healing 6
Using hyperbaric oxygen therapy without clear evidence of benefit for the specific patient (neuro-ischemic or ischemic ulcers where standard care has failed) is inappropriate 6
Neglecting cardiovascular risk reduction (smoking cessation, hypertension and dyslipidemia control, antiplatelet therapy) while focusing solely on local wound care misses the systemic nature of the disease 1, 7
Failing to educate patients about daily foot inspection and the importance of therapeutic footwear after healing leads to preventable recurrences 6