Following the rosiglitazone controversy there is a requirement from the licensing agencies that new antidiabetic drugs must be shown not to increase cardiovascular risk during phase 3 development. This includes studying patients with high cardiovascular risk, who were previously excluded from phase 3 studies. All of the currently available dipeptidyl peptidase (DPP)-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin) have satisfied these safety criteria, with the suggestion that there might be some cardiovascular benefit with this class. Large randomised-controlled trials are ongoing to assess safety as well as potential benefit. The results of these randomised-controlled trials will influence the long-term use of DPP-4 inhibitors and their place in treatment guidelines. Copyright © 2013 John Wiley & Sons.