(CR-017) Beta-adrenergic Antagonist for the Healing of Chronic Diabetic Foot

Mirabel Dafinone, BS; Johanna Ghebrehiwet-Kuflom, BS; Rawling Lyle, BS; Pallas Lim, BS; Anuj Budhiraja,, BS; Alisha Mehta, BS; Harrison Shawa, MD; Ramanjot Kaur, MD; Catherine Tchanque-Fossuo, MD; Anthony Gallegos, BS; Roslyn R Isseroff, MD

Introduction: Diabetic foot ulcers (DFUs) are a significant and growing public health issue, affecting millions of individuals with diabetes. Chronic DFUs often fail to heal with standard care, leading to prolonged disability, increased healthcare costs, and the risk of amputation. Current therapies focus mainly on infection control and offloading, with limited effectiveness in promoting healing. Topical timolol, a nonselective beta-blocker, has shown potential in improving circulation and reducing inflammation, two critical factors for wound healing. However, its efficacy in DFU treatment remains underexplored. This study aimed to evaluate the effectiveness and safety of topical timolol as an adjunct to standard care in chronic DFU healing.

Methods: This randomized, double-blind, controlled trial enrolled 108 patients with chronic DFUs from the VA Northern California Health Care System between 2018 and 2023. Forty-eight patients met inclusion criteria and were randomized to either the standard of care (SOC) group (n=27) or the SOC + timolol group (n=21). The primary endpoint was complete wound healing by week 14. Secondary outcomes included healing by week 31, time to closure, wound size reduction, and adverse events. Safety was monitored by serum timolol levels. Statistical analysis was conducted using Fisher’s exact test, Kaplan-Meier survival analysis, and Cox proportional hazards modeling.

Results: At week 15, 38% (n=8/21) of patients in the SOC + timolol group had healed, compared to 33% (n=7/27) in the SOC group (p=0.77). By week 30, 71% (n=15) in the timolol group had healed, compared to 48% (n=13) in the SOC group (log-rank test, p=0.081). Cox modeling indicated that patients receiving timolol had a significantly higher likelihood of healing by week 30 (hazard ratio [HR] = 2.88, p=0.027). Timolol also significantly reduced the mean time to healing at week 15 (5.8 vs. 9.2 weeks, p=0.015) and led to greater wound size reduction at weeks 14 and 31 (p< 0.05). Adverse events were similar between groups, with no cardiac events reported in the timolol cohort.

Discussion: Topical timolol was associated with improved healing rates, faster wound closure, and greater wound size reduction compared to standard care. These findings suggest that timolol may be an effective adjunct for the treatment of chronic DFUs with minimal adverse effects, supporting its potential in diabetic wound care.