A Narrative Review of Local Therapies in Diabetic Foot Ulcers: Promises, Limitations and Unmet Needs

Diabetic foot ulcers (DFUs) frequently remain open despite multidisciplinary standard care. Local therapies target different components of the wound microenvironment, but their comparative value and generalisability are uncertain.

To critically summarise evidence for seven local approaches-autologous leucocyte-platelet-fibrin patches, placenta-derived products, sucrose octasulfate dressings, fish skin matrices, hyperbaric oxygen therapy (HBOT), topical oxygen therapy (TOT) and negative pressure wound therapy (NPWT)-and to identify limitations and research priorities.

PubMed and the Cochrane Library were searched through 31 July 2026, supplemented by citation tracking. Randomised and prospective comparative studies, systematic reviews or meta-analyses, guidelines and economic analyses were eligible. The narrative synthesis followed SANRA-informed principles. Forty-one publications were included, among them 18 randomised trial reports.

An international trial of the leucocyte-platelet-fibrin patch reported healing at 20 weeks in 34% versus 22% with standard care. A meta-analysis of 11 placental-product trials reported complete healing in 66.9% versus 34.1% (risk ratio 2.00). EXPLORER reported 48% versus 30% closure with sucrose octasulfate at 20 weeks. In deep ulcers, ODIN reported 44% versus 26% healing with intact fish skin at 16 weeks. TOT meta-analysis suggested benefit (risk ratio 1.59), whereas HBOT trials were discordant and NPWT evidence was clinically supportive but low certainty. Severe infection, osteomyelitis and critical ischaemia were commonly excluded.

Several local therapies improve healing in selected DFUs, but none replaces debridement, offloading, infection control and vascular care. Product-specific selection, durable outcomes, head-to-head pragmatic trials, complex-ulcer populations and independent economic evaluation are priority needs.