Clinical evidence for metformin's survival benefit in head and neck squamous cell carcinoma (HNSCC) remains mixed, with both neutral and positive findings reported across retrospective studies.

Experimental models and early clinical trials suggest metformin may prevent malignant transformation of oral premalignant lesions by inhibiting mTORC1 signaling.

Our case series provides preliminary evidence that metformin may delay or prevent progression from laryngeal dysplasia to carcinoma in patients with a history of HNSCC.

Metformin maintains a favorable safety profile, supporting the rationale for future prospective clinical trials to validate its role in cancer prevention.

This longitudinal case series reports our ongoing experience with metformin, an oral antihyperglycemic drug, as a possible agent to halt the progression of dysplastic lesions to carcinoma, in those with previously treated head and neck squamous cell carcinoma (HNSCC).

Three patients were included who had laryngeal dysplasia (age 66.67 ± 7.09; range 59–73 years; 3 male) with a follow up time of 17 to 88 months. The average dose of metformin was 500 mg twice daily. Two patients showed complete or partial regression of the dysplastic mucosa, while the third demonstrated a worsening of dysplasia after he halted treatment for six weeks.

Metformin is a safe agent that has the potential to prevent progression of laryngeal dysplasia in patients with a history of HNSCC. Further studies are needed to verify and expand on this limited case series.

Dysplasia

Larynx

Metformin

© 2025 Published by Elsevier Inc.