The impact of topical insulin therapy vs normal saline on wound healing in patients with diabetic foot ulcers - a systematic review and meta-analysis

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Abstract

AIM: The aim was to evaluate the impact of topical insulin therapy vs normal saline on wound healing in adults with diabetic foot ulcers. BACKGROUND: Diabetic foot ulcers are among the most debilitating complications of diabetes, associated with high morbidity, risk of amputation, and significant healthcare costs. Insulin, beyond its glycaemic effects, exhibits regenerative and angiogenic properties that may support wound healing when applied topically. MATERIALS AND METHODS: A systematic review was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA 2020 guidelines. A literature search was conducted across a number of databases, including MEDLINE, CINAHL, PubMed, EMBASE, and clinical trial registries. Only randomised controlled trials (RCTs) comparing topical or locally injected insulin with standard wound care in adult diabetic patients were eligible. Risk of bias was assessed using the Cochrane RoB 1.0 tool. Meta-analyses were conducted using Review Manager (RevMan) 5.4, employing a random-effects model. The certainty of the evidence was assessed using the GRADE process. RESULTS: Sixteen RCTs met the inclusion criteria. No study reported the number of wounds healed. Meta analysis of 2 studies demonstrated that topical insulin therapy was associated with a statistically significant reduction in time to wound healing (MD: -6.05 days, 95% CI: -7.55 to 4.55; p < 0.00001), in favour of the insulin group. A narrative analysis of 2 further studies concurs with the findings of the meta-analysis. Meta-analysis of 10 studies showed a statistically significant difference in wound size reduction (MD: -3.39 cm2 (95% CI: -5.34 to 1.45; p = 0.0006), in favour of the insulin group, with a narrative analysis of 5 further studies, concurring with the findings of the meta-analysis. The certainty of the evidence is low or very low certainty evidence, as it was downgraded mainly for high or unclear risk of bias across multiple domains. CONCLUSIONS: Study findings show that topical insulin therapy may enhance wound healing in adults with DFUs. However, due to methodological limitations, inconsistent application of the intervention and outcome measures, yielding low or very low certainty evidence, definitive conclusions cannot be drawn. Therefore, further large, high-quality, multicentre trials are needed to validate the findings here.

Abstract as published, via PubMed.