Colorectal cancer has become a considerable cause of concern in patients with type 2 diabetes mellitus due to its rising prevalence. Use of antidiabetic drugslike insulin, sulfonylureas, dipeptidyl peptidase-4 inhibitors and glucose-dependent insulinotropic peptide analogues have been associated with high risk of different types of cancers. Contrarily, metformin has garnered significant attention in the prevention and treatment of cancer in diabetics owing to its beneficial effects. These include its efficacy in many colorectal cancer models as an anti-proliferative, chemo preventive, apoptosis inducing agent, adjuvant, and radio-chemosensitizer. These multiple effects of metformin can be ascribed to its ability to alter upstream and downstream molecular targets underlyingoxidative stress, inflammation, apoptosis, autophagy, cell cycle, metabolic homeostasis, and epigenetic regulation.

According to two companion case-control studies conducted in Italy and Spain, there was a positive relation between colorectal cancer and diabetes. In addition, metformin therapy was associated with a reduced risk of colorectal cancer as compared to increased risk with insulin.A case-control study showed 12% risk reduction of colorectal cancer in diabetics on intake of metformin for a year. Several meta-analysis comprising case control and cohort studies showed statistically significant reduction in occurrence of colorectal cancer in people who were on metformin therapy compared to those who were not administered metformin.

It has been suggested that the capability of metformin to decrease the incidence of colorectal cancer is likely due to its potential to intervene the development of colorectal polyps and adenomas either in type 2 diabetes patients or non-diabetic patients. A prospective, randomized, placebo clinical trial showed that compared to placebo, administration of metformin reduced the mean number of aberrant cryptic foci in non-diabetic patients. Another phase-III, double-blind, randomized, placebo controlled trialshowed that metformin use for 1 year was safe and effective in reducing the occurrence of total polyps (hyperplastic polyps plus adenomas) to 38% versus 56.5% with placebo and of adenomas to 30.6% versus 51.6% with placebo. Thus, metformin seems to be a promising option for preventing and treating colorectal cancer in diabetic and non-diabetic population.

Reference

1. Kamarudin MNA, Sarker MMR, Zhou JR, et al. Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects. J Exp Clin Cancer Res. 2019;38(1):491.