Topical therapies for diabetic foot ulcers: a systematic review and network meta-analysis

Diabetic foot ulcer (DFU) is a life-threatening complication associated with high amputation and mortality rates. While numerous topical therapies exist, their comparative efficacy and safety remain unclear. We aimed to compare the efficacy and safety of topical therapies for DFUs to identify optimal treatment strategies.

We searched PubMed, Embase, and CENTRAL from inception to February 1, 2025, for randomized clinical trials (RCTs) evaluating topical therapies for DFUs. We excluded non-topical interventions to ensure clinically relevant comparisons. A Bayesian network meta-analysis was performed. The primary outcome was wound healing rate.

We included 51 RCTs involving 6161 patients and 23 interventions. 12 topical therapies, including placenta-derived products, platelet-related products, ON101, epidermal growth factor, and tissue-engineered skin substitutes, significantly improved wound healing rates vs standard of care (SOC). Placenta-derived products showed the greatest efficacy (OR 7.85 (95% credible interval (CrI) 4.62 to 14.15)) and were the only intervention to significantly reduce adverse events vs SOC (0.25 (95% CrI 0.10 to 0.60)). No interventions differed significantly from SOC in time to wound healing, serious adverse events, or infections.

Placenta-derived products and other biological or advanced topical therapies may demonstrate greater efficacy than the SOC in facilitating the healing of DFUs. Nevertheless, the certainty of evidence for most comparisons remains in the low-to-moderate range. These findings suggest potential benefits in integrating these therapies into the management of DFUs. However, high-quality RCTs are necessary to verify long-term outcomes.