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Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study

Mueller SA, Elicin O, Monney B, Rau T, Pra AD, Sachs L, Ramos IC, Vassella E et al.

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 2025

25 participants

Abstract

PURPOSE: Research suggests that metformin may reduce tumor hypoxia, rendering it a potential radiosensitizer. This study investigated metformin's effect on hypoxia-associated gene expression in oral cavity squamous cell carcinoma (OCSCC).

METHODS: In this prospective trial, non-diabetic patients with OCSCC scheduled for curative surgery received preoperative metformin for 10 to 14 days. Tumor biopsies were taken before and after metformin treatment. Gene expression profiling was performed using RNASeq, emphasizing on hypoxia-associated signaling pathways.

RESULTS: Fifteen patients of 25 enrolled patients completed the study protocol and passed quality checks. No significant difference in gene expression was observed after adjustment for multiple testing. No significant changes were found in the hypoxia-associated hypoxia-inducible factor 1- alpha (HIF1A) pathway or in other signaling pathways associated with metformin reported in the literature.

CONCLUSION: This study does not support the hypothesis that metformin improves tumor hypoxia in OCSCC after 10 to 14 days of treatment.

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 25 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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