Abstract
All of the glucose-lowering agents available today for the treatment of diabetes resulted from the in vivo antidiabetic drug discovery approach. This is not surprising given the limited understanding of the biochemical basis of diabetes. With new developments in the elucidation of the biochemistry and physiology of diabetes, along with the ever-increasing number of drug discovery technologies, screening tests have shifted from in vivo to in vitro and from a cellular to a molecular level. However, there are concerns with this shift because diabetes, especially type 2 diabetes, has multiple and independent molecular defects and most of the molecular targets currently used await clinical validation. One approach (employed by Shaman) has used focused in vivo screening and has been successful in avoiding or minimising the drawbacks of in vivo testing, while maintaining the benefits. It is hoped that the combined use of in vivo and in vitro approaches will generate new breakthroughs in diabetes.