Scientific Online Resource System

Annual for Hospital Pharmacy

Overview and critical analysis of clinical trials data and epidemiological surveys proving complex mechanism and controversy of anti-tumorigenic activity of metformin

Tatyana Teneva, Ilko Getov


Metformin might influence tumourigenesis throughout AMPK- both indirectly, through the systemic reduction of insulin levels, and directly, via the induction of energetic stress. Indirectly, metformin exerts its antitumorigenic effects by activating LKB1 (a tumor suppressor protein) and its downstream target AMPK, which, in turn, suppresses the activity of the mammalian target of rapamycin (mTOR), a signaling pathway with a central role in cancer cell growth and cancer pathogenesis. Also it has been shown that AMPK phosphorylates tuberous sclerosis complex-2 (TSC-2) that in turns inhibits mTOR signaling. The induction of energetic stress, that essentially signifies lack of or decrease in available energy resources for the cell, activates AMPK, which results in inhibition of cell growth and proliferation. AMPK activation assists in adaptation to metabolic stress. There have been many clinical trials because of the interest in anti-cancer effects of metformin. In 2014 new research appearing in Proceedings of the National Academy of Sciences, USA suggests that activation of AMPK may actually fuel cancer growth. While meta-analyses of observational studies have shown a reduced risk of cancer among patients on metformin, a similar analysis of randomized controlled trials, lately found no relationship between metformin and cancer risk. A retrospective cohort study, investigating the association between use of metformin compared with other antidiabetes medications, proves that Metformin does not affect cancer risk.


Metformin; AMPK; mTO LKB1; antitumorogenic effect; clinical trials

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Tsilidis KK, Capothanassi D, Allen NE, et al. Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-to-treat trial. Diabetes Care. 2014;37(9):2522-32.

National Cancer Institute at The National Institute of Health Metformin: Can a Diabetes Drug Help Prevent Cancer?, April 2013

Kisfalvi K, Eibl G, Sinnett-Smith J, Rozengurt E. Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Research 2009; 69: 6539-45.

Researchers at the National Institute of Aging (NIA), a part of the National Institutes of Health (NIH) in the US, tested the type 2 diabetes drug metformin on the mice. 2.08.2013г.

Interview at the Biomed Central conference on Metabolism, Diet and Disease in May 2014 with Navdeep Chandel, PhD, a Professor of Medicine and Cell Biology

Kourelis TV, Siegel RD. Metformin and cancer: new applications for an old drug. Med Oncol. 2012 Jun;29(2):1314-27.

Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009 Aug;137(2):482-8.

Metformin inhibits aromatase expression in human breast adipose stromal cells via stimulation of AMP-activated protein kinase. march, 2010

WHO Model List of Essential Medicines 18th list (April 2013)

Could diabetes pill metformin work against aging? National Institute of Aging (NIA), a part of the National Institutes of Health (NIH) in the US, August 2, 2013



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