Regresar

Metformin: Beyond diabetes mellitus

Abstract:

In the last 60 years, metformin has been a firmly established hallmark in the treatment of diabetes mellitus (DM), with the majority of patients with this disease consuming this drug. Metformin is prominent for its anti-hyperglycemic and insulin sensitizing effects, acting fundamentally via inhibition of the mitochondrial respiratory chain and the activation of the AMPK pathway. Although these are the most notorious mechanisms of action of metformin, various effects have been described, with an important impact not only on DM, but also on disorders such as cancer and neurodegenerative diseases, among others. This review describes current findings related to metformin use in these disorders and the relevant mechanisms of action. The anti-neoplastic effects of metformin are related with AMPK activation along with inhibition of mTORC1, Rag GTPases, HIF-1, and UPR, disrupting cellular energetic metabolism, which hampers their survival and promotes apoptosis. On the other hand, metformin may have a potential neuro protective effect, as well as an influence on cognitive potentiation. The proposed mechanisms focus on changes in the metabolism of tau protein and the production of p amyloid, as well as modulation of neuro inflammation and oxidative stress in the neuronal microenvironment. Although the future of metformin is promising, clinical evidence remains inconclusive for its use in cancer or neurodegenerative diseases; yet hopes are abundant for extending its indications in the near future.