Metformin is a biguanide derived from the plant Galega officinalis. Originally synthesized nearly 100 years ago in 1922 (1), it has been used in humans for more than 60 years (2). Interestingly, and despite its long history, the mechanism of action of metformin is not well understood (2). A decrease in hepatic neoglycogenesis has been the most frequently highlighted action (3,4). Metformin can influence AMP-activated protein kinase and the fructose-1,6-bisphosphatase pathway, leading to a decrease in the AMP/ATP ratio and reducing the energy available for neoglycogenesis (4). Recently, however, it has been suggested that its main mechanism of action resides in the gastrointestinal (GI) tract (5). Using delayed-release metformin that acts predominantly in the gut, Buse et al. (5) found that, despite lower bioavailability, this formulation had greater efficacy than immediate- and extended-release...