New therapeutic approaches in type 2 diabetes

Abstract

Type 2 diabetes is a progressive chronic disease resulting from a dynamic interaction between defects in insulin secretion and insulin action. New molecules have recently been launched and many others are under clinical investigation. Besides classical sulfonylureas and glinides, new insulin secretagogues are now available, which target the incretin gut hormone glucagon-like peptide-1 (GLP-1). Indeed, oral incretin enhancers acting as antagonists of the enzyme DPP-4 (dipeptidylpeptidase-4), which inactivates natural GLP-1,and injectable incretin mimetics (exenatide) or analogues (liraglutide), which reproduce the actions of GLP-1 while resisting to DPP-4, represent new opportunities to stimulate insulin secretion, without increasing the risk of hypoglycaemia and weight gain. Among insulin sensitizers, metformin remains unequivocally the first drug of choice for the treatment of type 2 diabetes, whereas promising drugs as thiazolidinediones (glitazones) were recently challenged because of various safety issues. When insulin is required, insulin analogues, both short-acting and basal ones, may offer some advantages regarding better control of postprandial hyperglycaemia, reduced risk of hypoglycaemia and/or lower weight gain in patients with type 2 diabetes. Emphasis should be put on early detection and intensive management of type 2 diabetes, individualized glucose lowering treatments and goals, stepwise pharmacological strategy avoiding therapeutic inertia, and multiple cardiovascular risk--targeted approach.