The backbone of oral glucose-lowering therapy: time for a paradigm shift?

The complex array of metabolic abnormalities associated with type 2 diabetes provides a number of new targets for therapeutic intervention. Although the established oral glucose-lowering therapies, metformin and the sulfonylureas, continue to provide the backbone of therapeutic approaches, the thiazolidinediones (TZDs) also play an important role. Further, a new class of oral agents, the dipeptidyl peptidase-IV (DPP-IV) inhibitors, has recently become available with apparent utility in decreasing postprandial glucose excursions. This review examines how the TZDs and the DPP-IV inhibitors might integrate into current treatment strategies, considering not only glycemic goals, but also longer-term benefits such as durability of glycemic control, effect on metabolic parameters and cardiovascular outcomes. A practical approach is taken, reflecting potential clinical situations in which therapeutic intervention is required.