Glucose-6-phosphatase inhibitors for the treatment of Type 2 diabetes

Much biological knowledge has been gained over the years as to the role of glucose-6-phosphatase, (G-6-pase), enzyme complex in glucose homeostasis an d in Type 2 diabetes. Glucose-6-phosphatase is mainly located in the liver and catalyses the terminal step in both gluconeogenesis and glycogenolysis. Another interesting feature is that the enzyme activity is several fold hi gher in diabetic animals and probably also in diabetic humans and therefore could be an important key player in the elevated hepatic glucose productio n seen in Type 2 diabetes. During the last nine years substantial efforts h ave been made, primarily by scientists at Hoechst (now Aventis) and Novo No rdisk, in order to discover novel compounds which inhibit the glucose-6-pho sphatase enzyme complex and could be applied therapeutically in the treatme nt of Type 2 diabetes. These compounds, as well as other compounds publishe d with inhibitory action on glucose-6-phosphatase, are reviewed. No compoun ds yet have been reported to be in clinical development.