Abstract
Introduction: Colorectal cancer (CRC) is the second-leading cause of mortality and morbidity worldwide with multiple standard therapies that failed to improve outcomes. Metformin, an old, repurposed medication with pleiotropic effect in a number of cancers, arise as a possible treatment for CRC. This review aimed to assess the effect of metformin in addition to the treatment plan of CRC patients.

Methods: To identify relevant studies, Google scholar, PubMed, Egyptian knowledge bank (EKB) and clinical trial.gov were systematically searched. Pre-defined search keywords were used as “Metformin", “colorectal cancer", “randomized controlled trials", “interventional studies", “observational studies". Only English-based trials that are in full text were included.

Results: A total of 20 studies with different therapeutic adjuvant treatment options were evaluated for metformin treatment effect in CRC. Randomized control trials and observational studies were the main interest of the review while preventive and pre-clinical studies including animals and cell lines were excluded.

Conclusion: Most of the studies except few showed promising results on overall survival (OS), disease free survival, relapse-free time for metformin use as treatment in CRC. Also, a reductive effect of metformin was shown in toxicities as oxaliplatin-induced peripheral neuropathy and poor prognostic features as vessel co-option vasculature in liver metastasis. Future clinical randomized controlled studies are essential to confirm these results.