Metformin use was linked to lower odds of developing esophageal squamous cell carcinoma in a Nordic population–based case-control study, according to findings published by Xie et al in JAMA Network Open.
“This should prompt investigations of metformin as a preventive option in high-risk individuals and as a potential future therapeutic agent for esophageal squamous cell carcinoma,” the investigators commented.
Study Details
This analysis focused on data from Denmark, Finland, Iceland, Norway, and Sweden from 1994 to 2023. Investigators identified 13,050 patients newly diagnosed with esophageal squamous cell carcinoma (61.5% men; median age at diagnosis = 70 years) and matched each to 10 control participants, for a total of 130,500 controls, selected from the general population by age, sex, calendar year, and country.
Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between metformin use and esophageal squamous cell carcinoma. In addition to the matching, investigators adjusted the ORs for tobacco smoking, alcohol overconsumption, use of nonsteroidal anti-inflammatory drugs or aspirin, and use of statins. A dose-response analysis was performed among participants with at least 5 years of observation, based on defined daily dose over that period.
Metformin and Risk Reduction
Metformin use was found to be associated with a 36% reduction in the odds of developing esophageal squamous cell carcinoma compared with nonuse (OR = 0.64, 95% CI = 0.59–0.69). The investigators reported that the odds were particularly lower among high-dosage users (> 1,278 defined daily doses over 5 years; OR = 0.52, 95% CI = 0.44–0.61).
“The findings provide a rationale for exploring metformin as a preventive option in high-risk individuals; for example, those with precancerous lesions. The results also suggest a value of examining whether metformin medication after curative treatment for esophageal squamous cell carcinoma may improve survival,” the investigators commented.
They continued, “The value of examining metformin as a preventive or therapeutic target in selected individuals, even in those without diabetes, is supported by the good safety profile, wide availability, and low cost of the treatment. However, current evidence remains limited, and before metformin may be recommended for these purposes, additional observational research followed by randomized clinical trials are needed.”
Shao-Hua Xie, MD, PhD, of Karolinska Institutet, Stockholm, is the corresponding author of the article in JAMA Network Open.
Disclosure: The study was funded by the Swedish Research Council and the Swedish Cancer Society. The study authors reported no conflicts of interest.
