Metformin use linked to lower risk of esophageal cancer in Nordic study

A large multinational study across five Nordic countries found that metformin use was linked to lower odds of esophageal squamous cell carcinoma (ESCC), according to a study published in the JAMA Network Open in March 2026.

ESCC is a common and often deadly form of cancer, with fewer than 1 in 5 patients surviving five years. According to Mayo Clinic, esophageal cancer occurs when abnormal cells grow in the lining of the esophagus, the long tube that carries food from the throat to the stomach. It can develop anywhere along the esophagus and interfere with the normal movement of food to the stomach.

Metformin, a widely used and generally safe first-line treatment for diabetes, shows possible anticancer effects in several other cancers, raising interest in its role beyond blood sugar control. In the U.S., metformin is commonly known under the brand name Glucophage. It’s prescribed to treat type 2 diabetes by helping control blood sugar and improving how the body uses insulin, typically alongside diet and exercise changes, according to the Cleveland Clinic.

Globally, metformin is available under other generic and branded versions, including Axpinet, Diagemet, Fortamet and more. Beyond its role in diabetes care, metformin can also affect cancer-related pathways such as cell growth and inflammation.

Due to its low cost, long history of use and favorable safety profile, metformin has drawn attention as a possible option for cancer prevention and treatment, according to the study.

While some smaller studies have suggested that metformin can lower the risk of ESCC, the evidence has remained limited and unclear. To better understand this link, researchers from institutions across Sweden, Iceland, Denmark, Finland, Norway and the United Kingdom conducted a large population-based study using long-term health registry data.

The goal was to look at whether metformin use is associated with a lower risk of developing ESCC and to explore patterns across different patient groups and levels of drug use.

To do so, researchers conducted a population-based case-control study across Denmark, Finland, Iceland, Norway and Sweden from 1994 to 2023 using data from the Nordic Gastric and Esophageal Tumor Study. The study included all patients newly diagnosed with ESCC identified through national cancer registries and matched each case with 10 control participants of similar age, sex and calendar year who did not have esophageal cancer.

Multiple nationwide health registries using unique personal identification numbers were used, allowing researchers to track cancer diagnoses, medication use, medical conditions and survival over time. Metformin exposure was measured using prescription records, with patients considered users if they had at least two prescriptions before diagnosis to reflect longer-term use.

The long study period and large sample size allowed researchers to examine patterns over time and adjust for key risk factors such as smoking, alcohol use and other health conditions.

Overall, the study included 13,050 patients with ESCC and 130,500 matched control participants, with a median age of 70 years. It was found that patients with ESCC were more likely to have smoking- and alcohol-related conditions, while use of NSAIDs, aspirin and statins was similar between groups.

Metformin use was less common in ESCC patients than in control participants and was associated with a 36% lower odds of developing the cancer after adjustment. The results also showed a dose-response pattern, with higher doses of metformin linked to bigger risk reductions. For example, high-dose users had about a 48% lower chance of getting the disease. Additionally, results remained consistent after accounting for recent medication use.

The association between metformin and lower ESCC risk was also observed across all subgroups, including by sex, age and health history, but appeared stronger in adults ages 66 to 74 and those with smoking-related diagnoses.

Based on study design and its overall findings, the study’s strengths include its large population-based design, long follow-up period and use of high-quality registry data across five countries, which helped reduce bias and improve the reliability of the findings.

However, authors did note several limitations, including limited data on lifestyle factors such as diet and incomplete measures of smoking and alcohol use, as well as reliance on prescription records rather than confirmed medication use. The findings may not apply to populations outside of Western countries.

Based on the findings, the authors suggest that metformin should be further studied as a possible preventive option for people at high risk of ESCC and as a treatment after curative therapy but stressed that more research, including randomized clinical trials, is needed before it can be recommended in practice.