ESPE Yearbook of Paediatric Endocrinology

Brief summary: This review provides an update on the possible actions of metformin beyond glucose regulation in the liver. It summarizes recent findings regarding its action in the gastrointestinal tract, on gut microbiota and tissue-resident immune cells and thereby gives insight into studies addressing its immune-modulating and anti-inflammatory effects for possible use as treatment against inflammation- and age-related diseases, as well as cancer. Current knowledge of metformin’s several mechanisms of action at the molecular level is also summarized.

Metformin (1,1-dimethylbiguanide hydrochloride) was synthesized one hundred years ago and was found to lower blood glucose levels leading to its current widespread use as an medication in type 2 diabetes mellitus (T2D) as well as many other metabolic-related conditions. However, it remains a fascinating agent that is still extensively studied as its actions expand beyond the field of glucose regulation and the liver and reach the level of systems biology through its modulation of the inflammasome and immune system.

Will we all soon take metformin as a preventive treatment against aging and low-grade inflammation-related disorders? There are still many open questions to understand the complex actions and possible benefits of metformin.

It is also important to note that with thousands of people taking metformin, this compound is accumulating in our environment. Metformin is not metabolized in the human body but is excreted in urine and feces to reach waste waters. Out there it is biotransformed by microbial degradation and photolysis to numerous organic products that may endanger our global environmental health. Therefore studies of these aspects are also needed.

Of note: Same authors wrote an excellent review on metformin and glucoregulation in T2D in 2019 (1).

Reference: 1. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Foretz, M., Guigas, B. & Viollet, B. Nat. Rev. Endocrinol. 15, 569–589 (2019). DOI: 10.1038/s41574-019-0242-2.