A new study suggests that metformin may be associated with a reduced risk of developing non-melanoma skin cancers. The study examined outcomes across different demographic groups, including patients with skin of color.

A large propensity-matched case-control study—published in the Journal of Drugs in Dermatology—analyzed data from 4,111 squamous cell carcinoma (SCC) cases (matched to 16,444 controls) and 8,047 basal cell carcinoma (BCC) cases (matched to 32,188 controls). Cases and controls were matched by age, sex, race, and ethnicity.

"Our results indicate a reduced risk of non-melanoma skin cancer following exposure to metformin in individuals diagnosed with both SCC and BCC," the researchers reported.

For BCC, the univariable odds ratio (OR) was 0.46 (95% CI: 0.42-0.50), while the multivariable adjusted ORs were 0.37 (95% CI: 0.34-0.41) and 0.33 (95% CI: 0.29-0.36) after controlling for various confounders. Similarly, for SCC, the univariable OR was 0.65 (95% CI: 0.58-0.73), with multivariable adjusted ORs of 0.52 (95% CI: 0.46-0.58) and 0.45 (95% CI: 0.40-0.51).

However, the protective effect of metformin varied among demographic groups. In African American patients, metformin exposure was not significantly associated with a reduced risk of SCC (OR: 0.61, 95% CI: 0.28-1.22). The researchers noted that this discrepancy might stem from differences in SCC pathogenesis, such as chronic scarring and inflammation, in these populations.

The study builds upon prior research from Iceland and Taiwan, which reported mixed findings regarding metformin's protective role against non-melanoma skin cancers. The Icelandic study, for example, was limited by a homogenous cohort predominantly of white individuals.

Proposed mechanisms through which metformin may exert protective effects include activation of AMP-activated protein kinase, inhibition of the mTOR pathway, and promotion of cell cycle arrest. These actions hinder cancer cell growth and enhance the immune response against tumors.

Study limitations included reliance on electronic health records for prescription data, potential misclassification due to diagnostic codes, and a lack of detailed clinical information about skin cancer cases. The authors stated that further prospective research, particularly in diverse populations, is necessary to evaluate metformin’s chemopreventive potential.

The research was conducted using data from the All of Us research program, a National Institutes of Health initiative aimed at creating a diverse health database from over 1 million Americans, with a specific focus on historically underrepresented groups in biomedical research.

The authors declared having no competing interests.