The impact of metformin use on survival outcomes in colorectal cancer: A systematic review and meta-analysis.

[BACKGROUND] Emerging research indicates that metformin exerts anticancer activity across multiple malignancies, including colorectal cancer (CRC). Yet, its prognostic influence in CRC remains uncertain due to conflicting evidence. This study examines the relationship between metformin administration and prognostic outcomes among CRC patients.

[METHODS] A thorough literature search was undertaken across PubMed, Web of Science, Scopus, and Google Scholar. Eligible studies consisted of cohort designs that reported hazard ratios (HRs) for all-cause mortality (ACM), disease-free survival (DFS), overall survival (OS), cancer-specific mortality (CSM), or recurrence-free survival (RFS). Pooled estimates were generated using random-effects models.

[RESULTS] A total of 31 cohort studies encompassing 167,683 participants were analyzed. Metformin use was linked to lower ACM (HR=0.79, 95 % CI: 0.70-0.90), reduced CSM (HR=0.80, 95 % CI: 0.69-0.94), and improved OS (HR=0.79, 95 % CI: 0.70-0.90), with the benefits most evident in diabetic populations. Among non-diabetic patients, no meaningful association with CSM was identified (HR=0.96, 95 % CI: 0.84-1.10), whereas diabetic patients exhibited a significant reduction (HR=0.77, 95 % CI: 0.63-0.93). No effect was observed for RFS (HR=1.00, 95 % CI: 0.96-1.05), and DFS demonstrated only a non-significant trend toward improvement (HR=0.78, 95 % CI: 0.59-1.04). Considerable heterogeneity was present and evidence of publication bias was noted for DFS.

[CONCLUSION] Metformin use is reported to be associated with favorable prognostic outcomes in individuals with CRC, particularly among those with type 2 diabetes. However, its role in disease recurrence remains uncertain. Further randomized controlled investigations are required to validate these results and to establish their relevance in non-diabetic populations.