Title:Metformin (The Miracle Drug) Kinetics in Different Diseases such as Cancer
Volume: 20
Issue: 6
Author(s): Zahra Tolou-Ghamari*
Affiliation:
- Nutrition and Food Security Research Center, Deputy of Research and Technology, Isfahan University of Medical Sciences, Isfahan, Iran
Keywords:
Metformin, diabetes, cancer, Type 1, prescription, pharmacokinetics.
Abstract: Metformin, a miracle drug that was introduced a century ago, could be considered for various
aspects of diseases such as diabetes (type 1 and 2), cancer prevention or chemotherapy, metabolic
and neurodegenerative disease. It is well known that the frequency of cancer is higher in patients
with type 2 diabetes mellitus. This review aims to provide updated information regarding clinical
pharmacokinetics and the mechanism of action of Metformin in different diseases such as cancer.
Diabetes type 1 is another chronic autoimmune disease detected usually in early childhood due to
immune-mediated devastation of insulin-producing pancreatic beta-cells. Because of the lack of effective
therapeutic approaches, its prevalence is increasing. Regarding cancer, an estimated 19.3 million
new cancer cases and almost 10.0 million cancer deaths were reported in 2020 worldwide. By
50-60% bioavailability, the main route of metformin excretion is through urine. Its mechanism of
action is based on 1) initiation of adenosine monophosphate-activated kinase, 2) block proinflammatory
paths in perivascular adipose tissue, 3) decrease in monocyte-to-macrophage differentiation
in vascular tissues, and 4) improvement in endothelial function. Metformin induces adenosine
monophosphate-activated protein kinase signaling and suppresses gluconeogenesis. Antitumor properties
of Metformin include a decrease in reactive oxygen species generation and inducing autophagy.
In addition to glucose-lowering effects, Metformin has moderate anti-inflammatory and antioxidative
effects. It could improve lipid profile and reduce overweight individuals' body mass and
arterial blood pressure. In type 1 diabetes, Metformin reduces the requirement for daily insulin and
improves glycemia. Its long-term use decreases cardiovascular events. In addition to inhibiting the
synthesis of lipids via a reduction in oxidative stress, Metformin inhibits inflammation and increases
energy metabolism. Finally, by reducing micro- and macro-vascular consequences, mortality-related
diabetes and cancer decline by metformin administration. Therefore, in addition to diabetes, Metformin
could reduce the proliferation of cancer cells and the possibility of malignancies in different
types of cancer.
