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To determine whether the local administration of insulin glargine compared with placebo in nondiabetic patients with venous ulcers (VUs) leads to increased wound healing. A randomized controlled trial using a split-plot design was performed in 36 adults with leg VUs >25 cm2 and more than 3 mo of evolution. Each hemi-wound received either 10 UI insulin glargine or saline solution once a day for 7 d. Size of the wounds, thermal asymmetry, the number of blood vessels, and the percentage area of collagen content in wound biopsies were assessed at baseline and after 7 d of treatment. Blood capillary glucose was monitored once a day after the insulin injection. After 7 d of treatment, the hemi-wounds treated with insulin glargine were significantly smaller, had less thermal asymmetry, more blood vessels, and more collagen content than the saline-treated side. Correlation between thermal asymmetry and the number of blood vessels was also found (r2 = 66.2, P < 0.001). No patient presented capillary glucose levels ≤3.3 mmol/L nor any adverse effects. In nondiabetic patients with chronic VUs, the topical administration of insulin glargine seems to be safe and promotes wound healing and tissue repair after 7 d of treatment. [ABSTRACT FROM AUTHOR]