Efficacy of Topical Phenytoin in the Management of Diabetic Foot Ulcers: A Systematic Review.

Phenytoin has been used as an anti-seizure medication since 1939. There has been interest in its healing properties, with many randomized controlled trials (RCTs) investigating and recommending its use in diabetic foot ulcer (DFU) disease. Despite this, the International Working Group on the Diabetic Foot (IWGDF) does not support its use. The objective of this systematic review was to assess the use of phenytoin in the treatment of DFU disease compared to a control. Systematic searches of Medline, Embase, Google Scholar, the Cochrane Library, and ClinicalTrials.gov were conducted on January 5, 2024, using the keywords "phenytoin", "diabetes", "ulcer", and "RCT". Methodological quality was assessed using the Risk of Bias 2 (RoB 2) tool. A total of 23 studies were included in the systematic review, of which 20 recommended the use of phenytoin. However, the quality of the studies was poor. Of the included studies, 17 failed to implement blinding, 10 did not describe the randomization process, and only one completed a sample size calculation. There was a wide variation in both the study duration and the outcomes chosen to report the change in ulcer size. For this reason, a meta-analysis could not be performed. The current evidence does not support the use of phenytoin in DFU disease; further studies with larger patient numbers and reduced risk of bias are needed.