[Towards evidence-based medicine: large-scale intervention trials with dipeptidyl peptidase-4 inhibitors]

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antihyperglycemic drugs for the treatment of type 2 diabetes. They are also called "incretins" because they act inhibiting the degradation of endogenous incretin hormones, in particular glucagon-like peptide-1 that mediates their main metabolic effects. DPP-4 is a ubiquitous protease that regulates not only glucose and lipid metabolism, but also exhibits several systemic effects at different site levels. DPP-4 inhibition improves endothelial function, reduces the pro-oxidative and pro-inflammatory state, and exerts renal effects. These actions are mediated by different DPP-4 ligands, such as cytokines, growth factors, and neurotransmitters. Clinical and experimental studies have demonstrated that DPP-4 inhibitors are effective in protecting cardiac, renal and vascular systems, through antiatherosclerotic and vasculoprotective mechanisms. For these reasons, DDP-4 inhibitors should be considered "cardiovascular" as well as antidiabetic drugs. Clinical trials aimed at demonstrating that DPP-4 inhibitors are effective in reducing cardiovascular events, independent of their antihyperglycemic action, are ongoing. These trials will also provide necessary information on their safety.