Personalized approach for type 2 diabetes pharmacotherapy: where are we and where do we need to be?

Introduction: Cluster analysis has identified distinct groups of type 2 diabetes (T2D) subjects with distinct metabolic characteristics. Thus, personalizing pharmacologic therapy to individual phenotypic and pathophysiologic characteristics has potential to improve metabolic control and reduce risk of microvascular and macrovascular complications. Areas covered: The authors review the classification of T2D, genetic markers, pathophysiology and natural history of T2D, the ABCDE approach to therapy, the ADA/EASD stepwise approach to therapy, available antidiabetic agents, and provide a more rational therapeutic approach based upon pathophysiology and cardiovascular and renal outcome trials. Expert opinion: Although insulin resistance is the earliest detectable abnormality, overt T2D does not occur in the absence of progressive beta cell failure. Because of the complex etiology of T2D (Ominous Octet), initiation of therapy with combined agents that (i) target both insulin resistance and beta cell dysfunction and (ii) prevent macrovascular, as well as microvascular, complications will be required. The ratio of C-peptide at 120 minutes (OGTT) to baseline C-peptide predicts with high sensitivity who will respond to metformin, the response to glucose-lowering agents and provides a useful tool to guide optimal glucose lowering therapy.