Dipeptidyl peptidase-4 (DPP-4) inhibitors are one of two classes of antidiabetes drugs that mediate their glucose-lowering effect through the incretin pathway. They are administered orally and offer significant glucose-lowering with a neutral weight profile and a low risk of hypoglycaemia. Three large randomised-controlled trials have demonstrated cardiovascular safety, with no increase in major adverse cardiovascular events comparing DPP-4 inhibitors (saxagliptin, alogliptin and sitagliptin) with placebo. An increase in heart failure hospitalisation was noted with saxagliptin compared with placebo, and a similar increase was also noted in one subgroup receiving alogliptin compared with placebo. Further cardiovascular safety trials with DPP-4 inhibitors are ongoing, including a trial comparing the DPP-4 inhibitor linagliptin with the sulphonylurea glimepiride.