INS and Glucose intolerance: It has been pointed out earlier [36, 55] that, in order to make use of the potential antitumor and/or weight-reducing activities of metformin, it is necessary to consider its direct and indirect effects, the presence or absence of glucose intolerance, and impairments in the insulin/IGF-1 system and tissue responsiveness, which are determined, among others, by pharmacogenetic factors (see also [53, 63]).