Box 1, Figure 1.

Metformin reduces tumorigenesis through multiple mechanisms. The biguanide metformin, modeled after guanidine derivatives, was first isolated from the French lilac Galega officinalis. Currently, metformin is the most commonly used drug worldwide to treat patients with type 2 diabetes mellitus. Metformin suppresses liver gluconeogenesis, thereby reducing glucose release from the liver. Recently, metformin has been repurposed as an anticancer agent. There are two not mutually exclusive mechanisms by which metformin reduces tumor growth: (1) at the organismal level, in which it reduces the levels of circulating insulin, a known mitogen for cancer cells, and (2) in a cell-autonomous manner, by targeting mitochondrial electron transport at complex I. (Adapted from Birsoy et al. 2012, by permission from Macmillan Publishers Ltd.)