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Review
. 2025 Feb;398(2):1035-1055.
doi: 10.1007/s00210-024-03358-3. Epub 2024 Sep 3.

Metformin and the PI3K/AKT signaling pathway: implications for cancer, cardiovascular, and central nervous system diseases

Hemin Ashayeri Ahmadabad  1 , Somayeh Mohammadi Panah  2 , Hojat Ghasemnejad-Berenji  3 , Shabnam Ghojavand  4 , Morteza Ghasemnejad-Berenji  5   6 , Mohammad Rafi Khezri  7
Affiliations
Review

Metformin and the PI3K/AKT signaling pathway: implications for cancer, cardiovascular, and central nervous system diseases

Hemin Ashayeri Ahmadabad et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb.

Abstract

Recent findings have brought our understanding of diseases at the molecular level, highlighting upstream intracellular pathways as potential therapeutic targets. The PI3K/AKT pathway, a key regulator of cellular responses to environmental changes, is frequently altered in various diseases, making it a promising target for intervention. Metformin is the most known anti-diabetic agent that is known due to its effects on cancer, inflammatory-related diseases, oxidative stress, and other human diseases. It is clearly understood that metformin modulates the activity of the PI3K/AKT pathway leading to a wide variety of outcomes. This interaction has been well-studied in various diseases. Therefore, this review aims to examine PI3K/AKT-modulating properties of metformin in cancer, cardiovascular, and central nervous system diseases. Our findings indicate that metformin is effective in treating cancer and CNS diseases, and plays a role in both the prevention and treatment of cardiovascular diseases. These insights support the potential of metformin in comprehensive strategies for disease management.

Keywords: AKT; CNS; Cancer; Cardiovascular diseases; Metformin; PI3K.

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Conflict of interest statement

Declarations. Ethics approval: Not applicable. Conflict of interest: The authors declare no competing interests.

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