The Emerging Role of Metformin in Skin Cancer: Mechanistic and Clinical Insights.

BACKGROUND

Metformin, widely used for type 2 diabetes mellitus, has demonstrated antitumor effects through modulation of metabolic and immune pathways. This review explores its potential role in the prevention and treatment of skin cancers, including melanoma and nonmelanoma skin cancers (NMSCs).

METHODS

A structured PubMed search was conducted in April 2025 to identify English-language, peer-reviewed original research articles evaluating the effects of metformin on melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Experimental, observational, and clinical studies were included; reviews and meta-analyses were excluded.

RESULTS

Twenty studies met the inclusion criteria. In melanoma models, metformin inhibited tumor proliferation, suppressed epithelial-mesenchymal transition, and enhanced immune responses. Observational studies reported improved recurrence-free survival and treatment outcomes, although findings were inconsistent. In NMSC studies, metformin use was associated with reduced incidence of BCC and SCC. Preclinical models demonstrated delayed tumor development and an enhanced response to photodynamic therapy following metformin treatment.

DISCUSSION: Mechanistic and preclinical data support a biologically plausible role for metformin in skin cancer prevention and therapy. Evidence is strongest for BCC, particularly in enhancing photodynamic therapy and reducing incidence in at-risk populations. Melanoma studies suggest synergy with immunotherapy, but clinical results remain variable.

CONCLUSION

Metformin shows promise as a low-cost, well-tolerated adjunctive therapy in dermatologic oncology. Further prospective and controlled studies are needed to clarify its efficacy, optimize dosing, and identify populations most likely to benefit.