Multinational case-control study of the association of metformin use and development of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) carries a poor prognosis, stressing the need for preventive measures. A decrease risk of ESCC among metformin users has been suggested, but evidence is limited. A population-based case-control study in the 5 Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) investigated the association between metformin use and ESCC risk. The study included 13,050 newlly diagnosed ESCC patients diagnosed between 1994 and 2023 at a median age of 70 years (IQR 62-77), matched 1:10 by age, sex, calendar year with control participants randomly selected from the general population (n=130,500). In addition to the matching, ORs were adjusted for tobacco smoking, alcohol overconsumption, use of NSAIDs or aspiring, and use of statins. Metformin use was associated with a 36% lower odds of ESCC compared with nonuse (OR 0.64; 95% CI 0.59-0.69). The odds were especially lower in participants with a higher dosage of metformin. The authors conclude that these findings suggest that metformin use may have preventive potential against ESCC, which warrants further evaluation.