Impact of metformin on gastric adenocarcinoma survival: A Belgian population based study

Background: Preclinical studies have shown anticancer activities of metformin in gastric cancer and a recent epidemiological study showed a decrease in recurrence and mortality of gastric cancer in metformin users. This study aimed to assess the impact of metformin on gastric cancer survival in diabetic patients at a Belgian population level. Methods: We conducted an observational, population-based study by linking data of the Belgian Cancer Registry with medical claims data coming from the health insurance companies for patients diagnosed with stage I to III gastric adenocarcinoma between 2006 and 2012. Information on gastric cancer-specific deaths was retrieved from mortality records collected by regional governments. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) and cancer-specific mortality (CSS). Results: In our population of 371 patients, a reduction in all-cause mortality was observed in metformin users (adjusted HR = 0.73, 95% CI: [0.52; 1.01], p = 0.06) but not for cancer specific mortality (adjusted HR = 0.86, 95% CI: [0.56; 1.33], p = 0.50). Pre-diagnosis exposure to metformin was associated with a significant improvement in OS (adjusted HR = 0.75, 95% CI: [0.57; 0.98], p = 0.04) that was not significant for CSS (adjusted HR = 0.89, 95% CI: [0.62; 1.28], p = 0.52). Moreover, no dose-response relationship between metformin use and either all-cause or cancer-specific mortality was observed. Conclusion: In the first population based study of metformin use in gastric cancer adenocarcinoma patients with previous diabetes, our findings suggest that metformin use might improve overall mortality. However, no such association was found for cancer-specific survival. Additional studies in other populations are required.