Moisturizer formulations for diabetic foot xerosis: a systematic review and meta-analysis of randomized controlled trials

Background Foot xerosis in people with diabetes increases the risk of skin fissuring, ulceration and complications like amputation, sepsis and death. Preventive skin care is therefore important, yet evidence-based guidance on the most effective formulations remains limited. This systematic review aimed to identify effective ingredients and formulations to treat diabetic foot xerosis. Methods A literature search was conducted in Medline, Cinahl, Embase, CENTRAL and Scopus. Randomized controlled trials (RCTs) involving adults with diabetes and foot xerosis (without ulcers) that compared topical formulations were eligible. Reviewers screened studies, extracted data, assessed risk of bias and certainty of evidence in accordance with Cochrane Intervention Review standards. Outcomes included xerosis severity, skin hydration, skin barrier integrity and adverse events. Meta-analyses of RCTs were conducted. The review was registered in PROSPERO (CRD42024579919). Results Eleven articles reporting twelve RCTs were included. Functional creams (i.e., base formulations with added ingredients, most commonly humectants, intended to enhance their effect) significantly reduced xerosis severity compared with standard base formulations after both two weeks (standardized mean difference [SMD] -0.58, 95% CI -1.05 to -0.11) and four weeks (SMD -0.30, 95% CI -0.46 to -0.14). The certainty of evidence was moderate. Functional creams significantly increased skin hydration (SMD 0.31, 95% CI 0.11 to 0.52), although the certainty of evidence was low. Creams containing urea were more effective than standard base creams after four weeks (SMD -0.36, 95% CI -0.55 to - 0.17), with high-certainty evidence. Adverse events were rare and mild. Conclusions Functional creams, particularly those containing humectants and primarily urea, show greater efficacy than standard bases. However, high-quality randomized controlled trials with long-term outcomes such as risk of foot ulcers are warranted. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42024579919 , identifier CRD42024579919.