Effect of Metformin Use on Survival and Recurrence Rate of Gastric Cancer After Gastrectomy in Diabetic Patients: A Systematic Review and Meta-analysis of Observational Studies

Background: Gastric cancer (GC) is one of the most common worldwide cancers and causes of death. Various studies have investigated the effect of metformin on overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and recurrence rate in diabetic patients after gastrectomy, and their results have been contradictory. This meta-analysis aimed to evaluate the effect of metformin use compared to sulfonylurea compounds with OS, CSS, RFS, and recurrence rate after gastrectomy in diabetic patients.

Methods: We reviewed the Scopus, Google Scholar, PubMed, Web of Science, and Embassy databases until September 2022 based on appropriate MESH terms. All observational studies that evaluated the effect of metformin on survival in diabetic patients who underwent surgery for GC were included. The hazard ratio (HR) with a 95% confidence interval was used to estimate the effect size. The Egger test was used to evaluate publication bias.

Results: Overall, nine studies, including 245,387 GC patients who underwent surgery, were included. The use of metformin significantly increased the OS rate (HR: 0.81, 95% CI: 0.78, 0.86, P: 0.001, I: 4.5%), CSS rate (HR: 0.72, 95% CI: 0.63, 0.81, P: 0.011, I = 0%), and RFS rate (HR: 719, 95% CI: 0.524, 0.986, P: 0.001) and decreased the recurrence rate after gastrectomy (HR: 0.83, 95% CI: 0.77, 0.87, P: 0.001, I: 0%). The use of metformin was significantly associated with a greater increase in OS and CSS rate and a greater decrease in recurrence rate in the Asian population than in the Western population.

Conclusion: The use of metformin in diabetic patients with GC can be associated with improved OS, CSS, RFS, and reduced recurrence rate after gastrectomy, especially in the Asian population.