Metformin and anti-cancer effects: Systematic insights into its therapeutic potential

Abstract

Author(s): Nithesh Babu Ramesh*, Abinaya Srinivasa Rangan, Vimal Kumar Anandan Govindaraj, Suhail Aamir, Gnanadeepan Thirugnanam and Mahendra Kumar Kalappan

Background: Metformin is a very widely prescribed antidiabetic drug that has recently received broad attention for its potential anticancer properties. New evidence suggests multifarious effects of metformin on cancer cell metabolism, growth, and survival. Objective: The objective of this systematic review is to take a deeper look and synthesize available research into the anti-cancer effects of metformin, underlining its treatment potential across different types of cancers. Methods: A systematic literature search up to June 2024 in PubMed, Scopus, Medline, and EMBASE has been done. The literature search primarily includes clinical trials, pre-clinical studies, and meta-analyses on the examination of anticancer mechanisms and efficacy of metformin. Extracted data have been analysed according to the criteria, most importantly on how metformin would influence cancer incidence and rate of progression besides its effects on patient outcomes. Results: 1026 articles were identified, after inclusion and exclusion criteria only 28 research articles were included. Various antiproliferative mechanisms contributing to the antineoplastic effects of metformin have been described. Metformin exerts significant pro-apoptotic and antiproliferative effects in a variety of cancer cell lines, such as prostate, breast, and pancreatic cancers. Mechanistically, this suggests that metformin activates the AMP-Activated Protein Kinase pathway (AMPK), inhibits mTOR signalling, and impacts the insulin/insulin-like growth factor 1 axis to create a net antitumor effect. Clinical reports showed that the administration of metformin to diabetic and nondiabetic patients lowered cancer risk selectively. Conclusion: Metformin in adjunct cancer therapy has some promise; this is so because many studies support its potential to improve cancer treatment outcomes. Further studies should focus on establishing optimal dosing regimens, understanding patient variation of response, and carrying out largescale clinical trials that clearly define the role of metformin in oncology. The present systematic review underlines the need for integrative approaches to take full advantage of the therapeutic potential for the cure of cancer.

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