New approaches to the treatment of diabetes

Summary

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 1 and Type 2 diabetic patents in late stage clinical development. The 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 gluco-neogenesis.

To overcome peripheral insulin resistance, phosphoinositol-glycans were identified and synthesized showing insulinomi-metic activity on adipose and muscle tissue also in the insulin-resistant state in contrast to insulin.

Key words

Basal insulin - HOE 901 - hepatic glucose output - glucose-6-phosphatase - insulin resistance - phosphoinositol glycans - insulinomimetics