The development and benefits of metformin in various diseases

Abstract

Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.

Keywords

metformin / metabolism / cancer / aging / neurological disorder

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Acknowledgements

This work is founded by China Postdoctoral Science Foundation (No. 2021M703345), the National Natural Science Foundation of China (Nos. 82130099, 81971265, and 81821005), Shanghai Science and Technology Development Funds (Nos. 22YF1457100 and 22ZR1415200), National Key R&D Program of China (No. 2022YFA1303802), the National Natural Science Foundation of China for Innovation Research Group (No. 81821005), the Lingang Laboratory (Nos. LG202103-03-04, LG202103-03-01, and LG202103-03-05).

Compliance with ethics guidelines

Ying Dong, Yingbei Qi, Haowen Jiang, Tian Mi, Yunkai Zhang, Chang Peng, Wanchen Li, Yongmei Zhang, Yubo Zhou, Yi Zang, and Jia Li declare no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee

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