Metformin exerts anti-obesity effect via gut microbiome modulation in prediabetics: A hypothesis.

Prediabetic individuals are characterized by high levels of insulin, an anabolic hormone having an important role in the maintenance of glucose homeostasis. However, insulin has also been found to increase the growth of certain bacteria which form the non-butyrate producing part of the gut microbiome. The gut microbiome is recently in focus for its strong association with many chronic diseases such as type 2 diabetes mellitus and obesity. Metformin, a widely popular anti-diabetic medication has been shown to prevent weight gain in many trials. There are many studies postulating the mechanisms of the anti-obesity effect of metformin including improvement in insulin sensitivity (and consequently a reduction in insulin levels). Recently, however, it is becoming evident that metformin's action is likely to be primarily mediated by the gut. Further, metformin has also shown to affect the growth characteristics of certain bacteria which form the part of the human gut microbiome. With this frame of reference in mind, we hypothesize that metformin is likely to exert its anti-obesity effect by altering the composition of the gut microbiome. If proved, this has the potential to contribute to the management of obesity and pave the way for the development of novel anti-obesity drugs.