The Effect of Metformin on the Survival of Colorectal Cancer Patients with Type 2 Diabetes Mellitus

Abstract : Introduction: Colorectal cancer (CRC) is the second most deadly cancer worldwide and the third most diagnosed globally. Evidence from previous studies suggests a protective effect of metformin in patients with CRC. The aim of this study was to examine the associations between metformin use and overall survival (OS) and disease-free survival (DFS) in CRC patients with type 2 diabetes mellitus. Method: This was a historical cohort study. It included diabetic patients who underwent surgery for CRC at Limoges’ University Hospital between 2005 and 2019. Data on the characteristics of patients, CRC, comorbidities and drug exposure were collected from the patients’ electronic medical records. The exposure was the use of metformin. Patients were followed for two years after surgery. The outcomes were overall survival (OS) and disease-free survival (DFS). Multivariate analysis using the Cox model was performed and all statistical analyses were done with IBM SPSS Statistics 22. Results: Of the 1605 patients operated for CRC, 290 patients were identified with type 2 diabetes mellitus. Half of the diabetic patients were treated with metformin (49.7%). The 2-year OS rate for metformin users was 86.9±2.9% and 71.0±4.0% for metformin non-users (p=0.001). The Cox regression model showed a 64.0% reduction in all-cause mortality (adjusted hazard ratios (aHR), 0.36; 95% confidence interval 95%CI 0.17-0.73) among metformin users compared with non-users. Furthermore, metformin users had better DFS than non-users (aHR, 0.31; 95%CI 0.19-0.52). Conclusion: The use of metformin may improve OS and DFS in diabetic patients with CRC. Further prospective studies are also recommended to better explore the effect of this drug.