The most widely prescribed oral anti-diabetic agent today in the world today is 
a member of the biguanide class of drugs called metformin. Apart from its use in 
diabetes, it is currently being investigated for its potential use in many 
diseases such as cancer, cardiovascular diseases, Alzheimer's disease, obesity, 
comorbidities of diabetes such as retinopathy, nephropathy to name a few. 
Numerous in-vitro and in-vivo studies as well as clinical trials have been and 
are being conducted with a vast amount of literature being published every day. 
Numerous mechanisms for this drug have been proposed, but they have been unable 
to explain all the actions observed clinically. It is of interest that insulin 
has a stimulatory effect on cellular growth. Metformin sensitizes the insulin 
action but believed to be beneficial in cancer. Like -wise metformin is shown to 
have beneficial effects in opposite sets of pathological scenario looking from 
insulin sensitization point of view. This requires a comprehensive review of the 
disease conditions which are claimed to be affected by metformin therapy. Such a 
comprehensive review is presently lacking. In this review, we begin by examining 
the history of metformin before it became the most popular anti-diabetic 
medication today followed by a review of its relevant molecular mechanisms and 
important clinical trials in all areas where metformin has been studied and 
investigated till today. We also review novel mechanistic insight in metformin 
action in relation to microbiome and elaborate implications of such aspect in 
various disease states. Finally, we highlight the quandaries and suggest 
potential solutions which will help the researchers and physicians to channel 
their research and put this drug to better use.