New approaches to the treatment of diabetes

The underlying pathomechanism of the interdependent metabolic diseases diabetes, obesity and atherosclerosis is an imbalance of carbohydrate and lipid metabolism as well as energy homeostasis. The therapeutic goal for new medicines to treat metabolic diseases is thus the normalization and maintainance of macronutrient and energy homeostasis with drugs affecting transport, biosynthesis and signaling of carbohydrate and lipid pathways. The insulin analog HOE 901 is a new promising basal insulin for the treatment of Type I and Type 2 diabetic patents in late stage clinical development. Thc increased hepatic glucose production in type 2 diabetics can be normalized by novel inhibitors of the hepatic glucose-6-phosphate transporter of the glucose-6-phosphatase systems being the terminal step of hepatic glucose production from both, glcycogenolysis and gluconeogenesls. To overcome peripheral insulin resistance, phosphoinositolglycans were identified and synthesized showing insulinomimetic activity on adipose and muscle tissue also in the insulin-resistant state in contrast to insulin.