Prognostic role of metformin intake in diabetic patients with colorectal cancer: An updated qualitative evidence of cohort studies

Several observational studies have shown that metformin can modify the risk and survival of colorectal cancer (CRC) in patients with diabetes mellitus, although the magnitude of this relationship has not been determined. We conducted an updated systematic review and meta-analysis to analyze the association between metformin and CRC mortality and searched relevant databases up to July 2016. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CS) and disease-free survival (DFS). Summary hazard ratios (HRs) were calculated using a random-effects model. Seventeen studies enrolling 269,417 participants were eligible for inclusion. Comparing with non-metformin users in diabetic CRC patients, the summary HRs for OS in metformin users were 0.69 (95% CI, 0.61-0.77). Subgroup analyses stratified by the study characteristics and sensitivity analysis by the trimand- fill method (adjusted HR 0.77, 95% CI, 0.67-0.87) confirmed the robustness of the results. However, significant OS benefit was noted in patients with stage II and III disease. Five studies reported the CRC prognosis for CS and three for DFS; metformin intake was significantly associated with patient CS (HR 0.75, 95% CI, 0.59-0.94), but not DFS (HR 0.38, 95% CI, 0.13-1.17). Our findings suggest that metformin intake is associated with improved survival outcomes in terms of OS and CS in CRC patients with diabetes, particular for OS in stage II and stage III patients. Further studies should be conducted to determine CRC survival between metformin use and patient specific clinical and molecular profiles.