Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland

J Am Acad Dermatol. 2021 Jul;85(1):56-61. doi: 10.1016/j.jaad.2021.02.042. Epub 2021 Feb 19.

Abstract

Background: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed.

Objectives: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC.

Methods: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression.

Results: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96).

Limitations: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities.

Conclusion: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies.

Keywords: basal cell carcinoma; keratinocyte carcinoma; metformin; squamous cell carcinoma; squamous cell carcinoma in situ.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Basal Cell / epidemiology*
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Basal Cell / prevention & control
  • Case-Control Studies
  • Female
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / metabolism
  • Humans
  • Iceland / epidemiology
  • Male
  • Metformin / pharmacology
  • Metformin / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Skin / drug effects
  • Skin / pathology
  • Skin / radiation effects
  • Skin Neoplasms / epidemiology*
  • Skin Neoplasms / etiology
  • Skin Neoplasms / pathology
  • Skin Neoplasms / prevention & control
  • Ultraviolet Rays / adverse effects

Substances

  • Hedgehog Proteins
  • Metformin