JAMA Netw Open

Metformin linked to lower risk of esophageal squamous cell carcinoma

March 20, 2026

In this large, population-based case-control study, metformin use was associated with a substantially lower likelihood of developing esophageal squamous cell carcinoma (ESCC). Investigators analyzed data from more than 13,000 patients with newly diagnosed ESCC and 130,500 matched controls across five Nordic countries over nearly three decades. After adjustment for major confounders including smoking, alcohol use, and other medications, metformin use was associated with a 36% reduction in the odds of ESCC compared with nonuse (odds ratio, 0.64; 95% confidence interval, 0.59-0.69). The association appeared dose dependent, with the lowest odds observed among patients receiving higher cumulative doses over five years.

Clinical takeaway: For patients with diabetes who are at elevated risk for ESCC, consider continuing or preferentially selecting metformin when clinically appropriate, while recognizing that prospective trials are needed before metformin can be recommended specifically for cancer prevention.

Source:

Xie SH, et al. (2026, March 2). JAMA Netw Open. Metformin Use and Development of Esophageal Squamous Cell Carcinoma. https://pubmed.ncbi.nlm.nih.gov/41837999/