Metformin Use May Reduce Risk for Skin Cancer in Patients at Risk for Keratinocyte Carcinomas

Squamous cell carcinoma
Squamous cell carcinoma
The association between metformin and keratinocyte carcinoma in high-risk patients was evaluated.

Treatment with metformin was associated with a lower risk for skin cancer in patients at risk for keratinocyte carcinoma (KC), according to study findings published in Dermatologic Therapy.

The study was a survival analysis of the double-blind, multicenter Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial. In this trial, participants applied topical 5-fluorouracil (n=468) or vehicle control cream (n=464) twice daily to the face and ears for 4 weeks. Participants included individuals from 12 Veterans Affairs (VA) Medical Centers with 2 or more KCs in the 5 years before enrollment.

Most patients in the study were men (98%) and White (99%). The mean age of the cohort was 70 years, and the median follow-up duration was 2.8 years.

Independent predictors of squamous cell carcinoma (SCC) were prior invasive SCCs, number of prior SCCs in situ, body mass index, number of AKs at baseline, and age. In contrast, independent predictors of basal cell carcinoma (BCC) included the number of prior BCCs and age. The researchers noted that sunscreen use, history of sunburns, smoking history, and sun sensitivity were not significant predictors for a subsequent KC.

A total of 153 patients were prescribed metformin during the study. In the multivariable analysis, metformin users had a significantly lower risk for SCC (adjusted hazard ratio [HR], 0.45; 95% CI, 0.24–0.83; P <.01) and BCC (HR, 0.70; 95% CI, 0.47–0.97; P <.03).

Limitations of this analysis were the lack of data on drug interactions and duration of metformin exposure as well as the inclusion of mostly men. In addition, the enrollment of mostly White participants precludes the ability to determine whether metformin use also confers a lower risk for SCC and BCC in people with darker skin.

Based on these findings, the researchers of the study suggest “Metformin should be evaluated as a chemoprotective mean for a subsequent KC for high-risk patients.”


Misitzis A, Stratigos AJ, Beatson M, et al. The association of metformin use with keratinocyte carcinoma development in high-risk patients. Published online October 13, 2020. Dermatol Ther. doi:10.1111/dth.14402