SAT-584 - Topical Insulin as an Adjunctive Therapy Reverses Stalled Healing in Refractory Diabetic Foot Ulcers: A Case Series

Introduction
Diabetic foot ulcers (DFUs) are a major complication of diabetes associated with significant morbidity, often refractory to standard wound care. Systematic review and meta-analysis support topical insulin as an effective adjunctive therapy, demonstrating accelerated healing, reduced wound area, and improved granulation and angiogenesis compared with conventional care.

Case Presentation
The first patient was a 61-year-old man with poorly controlled type 2 diabetes mellitus (T2DM), hemoglobin A1c (HbA1c) 13.6%, and peripheral neuropathy who presented with a left first metatarsal head ulcer of 6 months duration. Initial treatment included serial debridement, amoxicillin-clavulanate for enterococcal infection, Iodosorb, Silvasorb, collagen powder, and delayed offloading with a knee walker due to logistical barriers. Healing stalled at a 56% reduction in wound area from baseline. Adjunctive topical insulin (10 units daily) was added alongside collagen powder, Silvasorb, and daily dressing changes, resulting in a 94% reduction in wound area from baseline within 30 days, with complete closure (100% area reduction from baseline) by day 132.
The second patient was a 75-year-old man with T2DM, HbA1c 8.1%, peripheral neuropathy, stage 3b chronic kidney disease, obesity, prior amputations, and osteomyelitis history, who presented with a chronic left heel ulcer of 22 months duration. Previous treatment included serial debridement, multiple courses of systemic antibiotics, and advanced wound care with Hydrofera Blue, medical honey, Silvasorb, Iodosorb, and collagen powder. Healing plateaued at a 73% reduction in wound area from baseline. Topical insulin (10 units daily) was added alongside collagen powder, Hydrofera Blue, and daily dressing changes, achieving complete closure (100% area reduction from baseline) within 84 days.
Neither patient experienced local or systemic adverse effects.

Discussion
This case series demonstrates accelerated healing of refractory DFUs following standard wound care failure. Randomized and comparative studies have shown faster wound closure, shorter healing time, and improved outcomes with topical insulin over conventional therapy. Mechanistically, insulin acts as a local growth factor, activating the PI3K/AKT and MAPK/ERK pathways and promoting keratinocyte migration, fibroblast proliferation, collagen synthesis, angiogenesis, and modulation of inflammation. Despite growing evidence, topical insulin remains underutilized, likely due to dosing variability and lack of standardized protocols.

Conclusion
As adjunctive therapy, topical insulin effectively overcame treatment-resistant healing plateaus in refractory DFUs after prolonged failure, reinforcing its role as a safe, low-cost, and underutilized option. Earlier integration into wound care protocols may improve outcomes in non-healing diabetic ulcers.

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