Foot xerosis, the clinical term for abnormally dry skin, is remarkably common in diabetes. Chronically elevated blood sugar impairs sweating, nerve function and the skin’s barrier machinery, leaving the stratum corneum, the outermost layer of the skin, parched and prone to cracking. Once cracks form, bacteria can enter, and in people with diabetes, whose immune defenses and circulation may already be compromised, a small fissure can spiral into a foot ulcer. Roughly 4 to 10 percent of people with diabetes develop such ulcers, and the lifetime risk may reach 34 percent. Despite this, patients are routinely told to apply foot creams without any firm guidance about which type, because most commercial products have never been evaluated specifically in the diabetic population.

The Swedish team, led by Karin Borgström, set out to close that gap with a review conducted to the exacting standards of Cochrane, the international benchmark for evidence synthesis. The researchers searched five major databases, Medline, Cinahl, Embase, CENTRAL and Scopus, without language or date restrictions, and screened 8,386 records before landing on 11 publications reporting 12 randomized controlled trials involving 603 participants and 949 feet. Only trials in adults with type 1 or type 2 diabetes and foot xerosis, but without existing ulcers, were eligible. The protocol was registered in advance on PROSPERO, and the team assessed risk of bias with the Cochrane RoB 2.0 tool and graded confidence in each result using the GRADE framework, a level of methodological rigor that previous reviews on the topic lacked.

The central comparison pitted functional creams, base formulations with added ingredients intended to enhance their performance, most commonly humectants such as urea and glycerol, against standard base creams lacking those additives. The distinction matters because these ingredient classes work through complementary mechanisms. Moisturizers form hydrophobic, occlusive films that reduce transepidermal water loss, while humectants attract and retain water within the stratum corneum and, intriguingly, keep the proteins and lipids of the skin barrier molecularly mobile even under dry conditions, preserving flexibility and barrier function beyond simple hydration.

The pooled results told a consistent story. After two weeks of treatment, functional creams significantly reduced xerosis severity compared with standard bases, with a standardized mean difference of -0.58, though heterogeneity between trials was high. By four weeks, the benefit persisted at -0.30 with zero heterogeneity, and the certainty of evidence was rated high. Skin hydration, measured by corneometry, also improved significantly with functional creams after both two and four weeks, although the certainty here was low, largely because studies measured hydration at different anatomical sites on the foot. Crucially, when the two trials judged to be at high risk of bias were excluded in sensitivity analyses, the effect remained significant and heterogeneity collapsed to zero, a sign the finding is robust rather than an artifact of flawed studies.

The single most striking result concerned urea. Across six studies, urea-containing creams beat standard base creams after four weeks with a standardized mean difference of -0.36, backed by high-certainty evidence. Even more compelling, two trials directly compared a urea, arginine and carnosine cream with glycerol-based products, one containing 40 percent glycerol and another 15 percent, and the urea formulation won decisively, with a standardized mean difference of -1.09 and high certainty. Urea was the most frequently studied humectant, which the authors caution may reflect research attention rather than proven superiority, but the head-to-head comparisons lend weight to the idea that urea offers something glycerol alone does not.

Not every comparison produced clear answers. A single study testing a plant-based anionic phospholipid emulsion, an emollient rather than a humectant, showed the smallest effect in the analysis, but one trial is too little to draw conclusions. Transepidermal water loss, a proxy for skin barrier integrity, fell significantly after two weeks in one trial but not at four weeks, and the data were too limited to judge. Adverse events across all trials were rare and mild, ranging from a transient burning sensation to one case of interdigital maceration judged probably treatment-related, an encouraging safety signal even if short follow-up periods temper firm safety claims.

The review also spotlighted an elegant trial design that much of this field relies on: the within-person, or split-foot, study, in which one foot receives the active cream and the other the control. Nine of the twelve trials used this approach, and it confers real statistical power by letting each participant serve as their own control, eliminating between-person variability. But it carries subtle risks, including cross-contamination when patients self-apply creams, baseline asymmetry between feet, and the possibility of unblinding when participants can feel or smell differences between products. The authors recommend objective outcome measures, such as corneometry, to guard against these biases, and their sensitivity analyses showed the pooled estimates barely moved when the design question was tested.

Perhaps the most sobering limitation is a structural one: the field lacks a common yardstick. Studies measured xerosis severity with scales ranging from 0-3 to 0-8, forcing the reviewers to use standardized mean differences, which express effects in standard deviation units that clinicians find hard to translate into practice. Urea concentrations varied from 5 to 25 percent, often alongside other ingredients, making it impossible to pin the benefit on urea itself or identify a dose-response relationship. No trial followed participants long enough to answer the question that ultimately matters most, whether better moisturized feet translate into fewer ulcers, amputations or deaths.

Even so, the practical message is clear and actionable today: for people with diabetes battling dry feet, a humectant-containing functional cream, ideally with urea, is a better bet than a plain emollient, and the evidence supporting that choice is now of genuinely high certainty for the four-week xerosis outcome. What comes next, the authors argue, is a new generation of adequately powered randomized trials with standardized formulations, agreed severity scales, prospective protocol registration and, above all, long-term follow-up tracking the outcomes that define diabetic foot disease. Given that the global diabetes population is projected to swell to 783 million by 2045, turning foot cream from folklore into evidence-based prevention could spare an enormous number of people from one of medicine’s most feared complications.

Subject of Research: Moisturizer efficacy for diabetic foot xerosis

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

Article References: Borgström, K., Björklund, S., Gudmundsson, P., Ericsson, A., & Acosta, S. (2026). Moisturizer formulations for diabetic foot xerosis: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Clinical Diabetes and Healthcare, 7, Article 1922860. https://doi.org/10.3389/fcdhc.2026.1922860

Image Credits: AI Generated

DOI: 10.3389/fcdhc.2026.1922860

Keywords: diabetes, diabetic foot, xerosis, moisturizer, urea, humectants, systematic review, meta-analysis, skin barrier, foot ulcers, skincare, randomized controlled trials