A review. Despite the availability of both monotherapies and combination therapies, the majority of type 2 diabetes (T2DM) patients fail to reach desired glucose levels and therefore are in need of new and more effective therapies. Fructose 1,6-bisphosphatase (FBPase), as the second-to-last enzyme in gluconeogenesis, controls the incorporation of all 3-carbon substrates into glucose, therefore, inhibition of FBPase should have reduced risk of hypoglycemia and other mechanistic toxicities. This chapter discusses the discovery of MB07803 as a second-generation FBPase inhibitor which could represent a potential candidate for the treatment of T2DM.