RE: Metformin Use and Gastric Cancer Risk in Diabetic Patients After Helicobacter pylori Eradication
Abstract
We read with great interest the article by Cheung et al. on the association between the use of metformin and the risk of gastric cancer in patients with type 2 diabetes following Helicobacter pylori eradication treatment (1). In their article, the authors reported that use of metformin was associated with a 51% reduction in the risk of gastric cancer (adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.24 to 0.98) compared with non-use of metformin. Although this study addresses an important question given the proposed anticancer effects of metformin, we think that the observed beneficial effects may be the result of immortal time bias. Immortal time refers to a period of follow-up during which, because of how the exposure is defined, the study outcome cannot occur (2). Indeed, the authors of the study defined metformin use as exposure to this medication for more than 180 days during follow-up, that is, the time between the index date (ie, H. pylori eradication treatment) and the end of the study period. Doing so, the authors gave exposed patients a “survival advantage” over the reference group, because they could not have experienced gastric cancer between the index date and the time point when they accumulated 180 days of metformin use. Importantly, immortal time bias has been previously examined in the specific setting of observational studies assessing the effects of metformin on the risk of cancer, where it was shown that it can lead to greatly…
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