Distinct effects of anti-diabetic medications on liver cancer risk and patient survival.

Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease worldwide. Multiple types of cancer, particularly liver cancer, are closely associated with T2DM. As a result, there is growing interest in investigating whether anti-diabetic medications could lower cancer risks in the population and even prolong patient survival among those with concurrent cancer. There are many types of anti-diabetic medications available in the clinic. The present study reviewed how different anti-diabetic drugs affect cancer risk and patient survival. On the one hand, multiple retrospective studies have shown that the different anti-diabetic medications have distinct effects on cancer risks. Insulin-raising drugs, including exogenous insulin, increased cancer risks, while drugs potentiating insulin sensitivity like metformin reduced cancer risks. On the other hand, the effects of anti-diabetic medications on patient survival are relatively less studied, except limited reports in liver cancer and pancreatic cancer. It seems that metformin could extend overall survival in patients of early-stage cancer. In contrast in the advanced cancer with metastasis, metformin has no effect or even worsens cancer mortality. It is yet unknown whether these distinct effects of metformin are attributable to the severity of the cancer staging or to the drug interactions between metformin and other medications. This question warrants reconsideration of the current clinical practice in the control of T2DM. Future large-scale prospective studies are needed to resolve this.