In addition to their glucose-lowering properties, incretin-based therapies have apparently beneficial effects on CV risk factors, accompanied by small effects on heart rate, without clinically meaningful QTc prolongation. There is mechanistic evidence to suggest that GLP-1 receptor agonists may confer cardioprotective effects following ischaemia. Retrospective MACE analyses conducted for the different incretin based therapies have been reassuring. However, as mandated by regulatory agencies, the long-term CV safety of DPP-4 inhibitors and GLP-1 receptor agonists is currently under investigation in large CV outcomes trials. The results – which will emerge over the next few years – may also provide data on the efficacy of incretin-based agents in preventing CV events. This information will supply the evidence needed to position the use of these classes rationally amongst other more established glucose-lowering therapies.