Topical metformin in wound healing: a comprehensive systematic review of therapeutic outcomes

Metformin's topical application has proven to be a therapeutic wound healing dressing via pro-angiogenic, anti-inflammatory, autophagy-promoting, and antibacterial effects. The systematic review article aimed to evaluate the available evidence (from both preclinical and clinical studies), in order to better understand its therapeutic potential in wound care. We performed a systematic literature search in PubMed, Scopus, Web of Science, Embase, and Cochrane databases till January 2025. A total of 26 studies included in final analysis according to inclusion criteria. The majority of preclinical investigations demonstrated accelerated wound healing with characterized of increased wound closure and collagen deposition, elevated pro-angiogenic markers (e.g., VEGF, CD31, and α-SMA), suppression of pro-inflammatory cytokines, and induction of autophagy signaling. Notably, biomaterial-based delivery platform applications such as hydrogels and nanofibers greatly magnified these therapeutic effects. While encouraging results in in-vitro, in-vivo and animal models have been documented, clinical studies remain limited in scope. In fact, this large disparity between preclinical results and limited clinical evidences obviously highlights the urgent need for properly designed human trials to determine safety, efficacy, and best delivery modalities of topical metformin. Collectively, topical metformin is a novel and potentially valuable addition to wound treatment cares, which could be subjected to further clinical study.