Metformin as a protective agent against natural or chemical toxicities: a comprehensive review on drug repositioning



Metformin is the first prescribed drug for hyperglycemia in type 2 diabetes mellitus. Mainly by activating AMPK pathway, this drug exerts various functions that among them protective effects are of the interest.


Herein, we aimed to gather data about the protective impacts of metformin against various natural or chemical toxicities.


An extensive search among PubMed, Scopus, and Google Scholar was conducted by keywords related to protection, toxicity, natural and chemical toxins and, metformin. Our literature review showed metformin alongside its anti-hyperglycemic effect has a wide range of anti-toxic effects against anti-tumour and routine drugs, natural and chemical toxins, herbicides and, heavy metals.


It is evident that metformin is a potent drug against the toxicity of a broad spectrum of natural, chemical toxic agents which is proved by a vast number of studies. Metformin mainly through AMPK axis can protect different organs against toxicities. Moreover, metformin preserves DNA integrity and can be an option for adjuvant therapy to ameliorate side effect of other therapeutics.

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Fig. 1
Fig. 2





Superoxide dismutase


Glutathione peroxidase






Aspartate aminotransferase


Alanine transaminase


Creatinine phosphokinase




Lactate dehydrogenase


Reactive oxygen species


Serum C-type natriuretic peptide


Total antioxidant capacity


Luteinizing hormone


Follicle-stimulating hormone


Nitrite oxide synthase


Polychromatic erythrocytes


Normochromatic erythrocytes


Bronchoalveolar lavage fluid


Nicotinamide adenine dinucleotide


Advanced glycation endproducts


AMP-activated protein kinase


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Meshkani, S.E., Mahdian, D., Abbaszadeh-Goudarzi, K. et al. Metformin as a protective agent against natural or chemical toxicities: a comprehensive review on drug repositioning. J Endocrinol Invest 43, 1–19 (2020) doi:10.1007/s40618-019-01060-3

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  • Metformin protection
  • Toxin
  • Natural toxin
  • Chemical toxin