Preventive Role of Metformin Against Hepatocellular Carcinoma in Patients with Diabetes Mellitus - A Systematic Review

Diabetes mellitus (DM) and hepatocellular carcinoma (HCC) are very challenging health conditions. Although the relation between them is not completely understood, many factors contribute to this relation, including hyperinsulinemia, inflammatory reactions, and other co modifiers as obesity. This study is designed to detect the role of metformin in preventing HCC in patients with DM compared to other anti-diabetic medications. We have screened the articles systemically in three databases such as PubMed, PubMed Central (PMC), and Medical Literature Analysis and Retrieval System Online(MEDLINE), using specific keywords and Medical Subject Heading (MeSH) terms for related published articles. Moreover, we have used Google Scholar, International Diabetes Federation (IDF), and American Diabetes Association (ADA). We have applied our inclusion/ exclusion criteria, and we have also applied the quality check assessment using Cochrane bias assessment, AMSTAR checklist, SANRA checklist, and New-Castle Ottawa tool. In the end, we reviewed ten studies that were strictly reviewed and analyzed. Based on our study, we reported that the major factor in the development of HCC in patients with DM is the duration, especially more than ten years. We concluded that the risk of development of HCC is directly proportional to the longer duration of DM. Our results show that metformin plays an important role in preventing HCC in patients with DM by decreasing insulin resistance. In contrast, the use of Insulin and drugs that promote insulin secretion is associated with increased incidence of HCC.