Metformin: a review of its potential indications

Yi-Wei Wang, Si-Jia He, Xiao Feng, Jin Cheng, Yun-Tao Luo, Ling Tian, Qian Huang, Yi-Wei Wang, Si-Jia He, Xiao Feng, Jin Cheng, Yun-Tao Luo, Ling Tian, Qian Huang

Abstract

Metformin is the most commonly prescribed drug for type 2 diabetes mellitus. In recent years, in addition to glucose lowering, several studies have presented evidence suggesting some potential role for metformin, such as antitumor effect, antiaging effect, cardiovascular protective effect, neuroprotective effect or an optional treatment for polycystic ovary syndrome. This paper will critically review the role of metformin to provide reference for doctors and researchers.

Keywords: PCOS; antiaging effect; antitumor effect; cardiovascular protective effect; metformin; neuroprotective effect.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Model of the ancient pathway by which metformin extends lifespan and inhibits growth. Notes: The figure shows that metformin’s suppression of mitochondrial respiratory capacity reduces cellular energy, restricting transit of the RagA-RagCGTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the guanosine diphosphate-bound state necessary to active mTORC1, subsequently inhibiting growth through transcriptional induction of ACAD10. Abbreviations: NPC, nuclear pore complex; ACAD10, acyl-CoA dehydrogenase family member-10.
Figure 2
Figure 2
Metformin targets multiple pathways of oncogenesis and aging. Notes: The figure schematically depicts the pathways that are important to target oncogenesis and aging, and indicates at which points metformin has been shown to have effects. These processes jointly affect cellular survival, antioxidation, inflammation, autophagy and protein synthesis, which are major biological outcomes associated with oncogenesis and aging/longevity. The green background means that metformin has a negative effect on the step. The yellow background means that metformin has an active effect on the step. Abbreviations: IGF-1R, insulin-like growth factor 1 receptor; IR, insulin receptor; ROS, reactive oxygen species; AMPK, AMP-activated protein kinase.
Figure 3
Figure 3
The linkage of the potential indications of metformin. Abbreviations: NPC, nuclear pore complex; ACAD10, acyl-CoA dehydrogenase family member-10; AMPK, AMP-activated protein kinase; SHBG, sex hormone binding globulin; PCOS, polycystic ovary syndrome.

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