Opinion Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2021; 27(14): 1362-1368
Published online Apr 14, 2021. doi: 10.3748/wjg.v27.i14.1362
How far along are we in revealing the connection between metformin and colorectal cancer?
Maja Cigrovski Berkovic, Danko Mikulic, Ines Bilic-Curcic, Anna Mrzljak
Maja Cigrovski Berkovic, Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
Maja Cigrovski Berkovic, Clinical Hospital Dubrava, Zagreb 10000, Croatia
Danko Mikulic, Department of Surgery, Merkur University Hospital, Zagreb 10000, Croatia
Ines Bilic-Curcic, Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
Ines Bilic-Curcic, Clinical Hospital Center Osijek, Osijek 31000, Croatia
Anna Mrzljak, Department of Medicine, Merkur University Hospital, School of Medicine, Zagreb 10000, Croatia
Author contributions: Cigrovski Berkovic M made contributions to the conception and design of the study and drafted and revised the manuscript critically; Mikulic D, Bilic-Curcic I, and Mrzljak A were involved in collecting data and drafting and writing the manuscript; all authors read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Anna Mrzljak, MD, PhD, FEBGH, Associate Professor, Department of Medicine, Merkur University Hospital, School of Medicine, Zajčeva 19, Zagreb 10000, Croatia. anna.mrzljak@gmail.com
Received: December 23, 2020
Peer-review started: December 24, 2020
First decision: February 11, 2021
Revised: February 14, 2021
Accepted: March 17, 2021
Article in press: March 17, 2021
Published online: April 14, 2021

Colorectal cancer (CRC) is among the most prevalent cancers worldwide, and its prevention and reduction of incidence is imperative. The presence of diabetes has been associated with a 30% increased risk of CRC, likely through the mechanism of hyperinsulinemia, which promotes tumorigenesis via the insulin receptor in the epithelium or by insulin-like growth factor pathways, inflammation, or adipokines, inducing cancer cell proliferation and cancer spread. Metformin, the first-line agent in treating type 2 diabetes, has a chemopreventive role in CRC development. Additionally, preclinical studies suggest synergistic effects of metformin with oxaliplatin in inhibiting in vitro models of colon cancer. Although preclinical studies on the post diagnostic use of metformin were promising and suggested its synergistic effects with chemotherapy, the data on the possible effects of metformin after surgery and other CRC treatment in the clinical setting are less conclusive, and randomized controlled trials are still lacking.

Keywords: Metformin, Type 2 diabetes mellitus, Colorectal cancer, Chemoprevention, Recurrence-free survival, Surgery

Core Tip: Metformin is one of the oldest oral antidiabetic agents used to treat type 2 diabetes mellitus. While there is substantial evidence that metformin may have a chemopreventive role in colorectal cancer (CRC) development, the data on the possible effects of metformin after surgery and other CRC treatment is much less conclusive.