Intralesional Insulin for the Treatment of Keloid and Hypertrophic Scars: A Systematic Review of Efficacy and Safety

Abstract

Background: Keloids and hypertrophic scars are fibroproliferative disorders characterized by excessive collagen deposition, persistent inflammation, and dysregulated remodeling. Conventional intralesional and procedural therapies (for example, corticosteroids, 5-fluorouracil, laser-based modalities, and adjuvant surgery) can reduce scar thickness and symptoms but are limited by recurrence, variable response, pain, pigmentary change, and atrophy. Insulin, beyond metabolic regulation, has recognized growth-factor–like effects in skin, influencing angiogenesis, fibroblast activity, and matrix turnover. These properties have generated interest in locally administered insulin as a scar-modulating intervention, including intralesional injection for established keloids and “intra-wound” insulin during repair or dressing as an approach to prevent hypertrophic outcomes. Objective: To systematically identify and qualitatively synthesize clinical evidence on local insulin administration (intralesional, intradermal/subcutaneous to incision margins, or intra-wound application) for efficacy and safety outcomes relevant to keloid and hypertrophic scarring, including mechanistic clinical endpoints (angiogenesis/fibrosis) plausibly linked to scar remodeling. Methods: A PRISMA 2020–guided systematic search strategy was applied across major bibliographic databases and supplementary citation searching. Eligible studies were prospective or retrospective human clinical studies evaluating local insulin administration with outcomes including keloid/hypertrophic scar response, scar appearance scores, or histologic/physiologic endpoints tied to fibrosis/angiogenesis and clinically relevant safety outcomes. Risk of bias was appraised using RoB 2 for randomized designs and ROBINS-I for nonrandomized studies, and findings were synthesized narratively due to heterogeneity. Results: Nine studies met inclusion criteria. Direct evidence in established keloids consisted of one three-arm comparative clinical study showing meaningful volume reduction across arms and superior performance of insulin versus botulinum toxin A on several scar domains, while corticosteroids and insulin were comparable on key endpoints. Evidence in scar appearance modulation included one randomized controlled breast-surgery trial reporting improved scar appearance with low-dose insulin injections, particularly in heavier scars. A small retrospective series suggested feasibility of insulin used during wound management with follow-up without prominent hypertrophic outcomes. Across wound and ulcer studies, local insulin consistently increased angiogenesis and granulation-related metrics, with mixed signals regarding fibrosis (increased in diabetic wound split-site biopsy studies), underscoring a potentially double-edged mechanism. Safety signals were generally reassuring, but clinically meaningful systemic absorption and symptomatic hypoglycemia were reported in at least one diabetic foot ulcer injection study, supporting individualized dosing and glucose monitoring. Conclusion: The clinical evidence base for intralesional insulin in keloids is promising but currently sparse, while broader local-insulin literature supports biologic plausibility for scar modulation through vascular and matrix pathways. Larger, rigorously controlled scar-specific trials with standardized scar scales, longer follow-up, and explicit safety monitoring are required before local insulin can be recommended as a routine first-line therapy for keloid or hypertrophic scars.