A Randomized, Double-Blind, Placebo-Controlled Trial to Determine the Effects of Topical Insulin on Wound Healing

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Omid Rezvani, MD; Elahe Shabbak, MD; Abolfazl Aslani, PhD; Ramin Bidar, MD; Mehrdad Jafari, MD; and Saeed Safarnezhad, MD

Abstract: Although the literature contains evidence demonstrating the beneficial effects of insulin on wound healing, no suitable method for the routine administration of insulin has been reported. A randomized, double-blind, placebo-controlled trial was conducted to determine the safety and efficacy of topical insulin on healing in 45 patients (29 men, mean age for both groups 40.62 years, range 12 to 71 years) with noninfected acute and chronic extremity wounds. Patients were randomly assigned to twice-daily topical application (spray) of 1 cc saline 0.9% for each 10 cm2 of wound with or without 10 units (0.1 cc) of insulin crystal and insulin. The endpoint was complete wound closure. Systemic glucose levels were measured before and 1 hour after treatment application. No patients developed signs or symptoms of hypoglycemia and glucose levels pre- and post-application did not differ significantly. Time to healing did not differ significantly between treatment groups. Healing rates were affected by baseline wound area, patient age, wound type (acute versus chronic), and treatment group. The mean rate of healing rate was 46.09 mm2/day in the treatment and 32.24 mm2/day in the control group (P = 0.029), independent of baseline wound size. In this study, the topical application of insulin was safe and effective. Clinical studies with a larger sample size and that include patients with diabetes mellitus are warranted.

Key Words: controlled clinical study, topical, insulin, wound healing

Potential Conflicts of Interest: Drs. Rezvani and Shabback received a research grant from EXIR Pharmacological, Iran.

Please address correspondence to: Omid Rezvani MD, Department of Plastic Surgery and Burn Care, Esfahan University of Medical Sciences, 79 Sarabchi, Molasadra St, Esfahan, Iran; email: omidrezvani@aol.com.





     Since Bunting’s discovery of insulin in 1921,1 many benefits beyond blood glucose regulation have been documented.2-4 Preclinical and clinical studies have demonstrated positive effects of insulin on wound healing,5-10 but no suitable method for routine clinical use of topically applied insulin has been reported.

     Wound healing is a complex biological process influenced by several agents such as insulin-like growth factor (IGF) and human acidic fibroblast growth factor (rh-aFGF).11 In vivo studies have shown that IGF can stimulate the proliferation and differentiation of endothelial cells and fibroblasts and promote granulation tissue regeneration to contribute to wound healing.12-14

     Many therapeutic methods are available to effect wound healing such as skin grafts, hydrocolloid dressings, and high-protein diets, but some may not be economically suitable for the patient and/or may be associated with complications.15-18 Similarly, the cost of methods such as negative pressure wound therapy may be prohibitive for many patients.20-28 A less clinically and economically complicated approach to healing chronic wounds seems necessary.

     The purpose of this controlled clinical study was to evaluate the safety and efficacy of topical insulin in patients with acute and chronic wounds.

Materials and Methods

     Setting and population. This study was conducted at Esfahan University of Medical Sciences and affiliated hospitals (Department of Dermatology, Alzahra, Musa-Kazem, and Shariati hospitals) and private clinics over a period of 18 months (April 2006 to October 2007). Forty-five consecutive in- and outpatients with skin wounds attending these hospitals and private clinics were enrolled in the study.

References: 

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