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OBJECTIVES: Esophageal cancer is a highly fatal malignant neoplasm, with 2 etiologically different histological types. A large prospective study is expected to elucidate the specific risk of the 90% subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC), with metformin therapy. This study aims to determine the association between metformin use and incident ESCC risk.
METHODS: This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified in the cohort, 411,603 (5%) were metformin users. The users were compared with 10 times as many frequency-matched nonusers of metformin (n = 4,116,030) by age and sex. Metformin use was treated as a time-varying variate, and multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for ESCC, adjusted for age, sex, calendar year, residence area, tobacco smoking, alcohol overconsumption, and use of nonsteroidal anti-inflammatory drugs or statins.
RESULTS: The incidence rates of ESCC were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the nonusers. Metformin users overall were at a decreased risk of ESCC compared with nonusers (HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users (HR 0.44, 95% CI 0.28-0.64) and participants aged 60-69 years (HR 0.45, 95% CI 0.31-0.66).
DISCUSSION: Metformin use decreases the risk of developing ESCC.
|Family Medicine (FM)/General Practice (GP)|
|General Internal Medicine-Primary Care(US)|
|Oncology - Gastrointestinal|
This paper suggests that metformin may decrease cancer. Since there was no information that metformin increased esophageal cancer, this paper will have no impact on clinical practice, which is why I rated it as not very relevant. It`s a little disingenuous to emphasize a distinction for this paper because it focused on one type of esophageal cancer that comprises 97% of the cancers. Including both types would not have changed the results.
A HR of 0.66 is modest for an epidemiologic study to rule out confounding by unmeasured and unimagined confounders. This is a hypothesis-generating article.
There are important methodologic limitations in this study. Metformin users were compared with non-metformin users, regardless of whether they had diabetes and with no adjustment for diabetes status or other anti-hyperglycemic agents.
This information needs to be validated by further study, preferably prospective randomized trials to ensure effectiveness and safety.
Interesting study. I won't be prescribing metformin for prevention of esophageal cancer, though.
This is a novel finding of a protective effect for a commonly used medication. It would be interesting to see this replicated in other databases.
The authors showed a small reduction in squamous cell carcinomas of the esophagus with metformin use in this large observational study. As a practicing oncologist, this information is of little clinical value. The benefit seen is small and the association is not proof of a cause-and-effect. Large randomized trials are needed, which is not likely. One may be somewhat reassured that the risk is not higher with metformin use.