It is well known that type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular diseases (CVD). A predicted worldwide increase in the incidence of T2DM, taking the form of an epidemic, is expected to induce a substantial increase in CVD incidence. Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are related to an increased risk of developing T2DM, especially in obese people. Prevention of T2DM aiming to reversal of pre-diabetes to normal glucose tolerance seems to be a very attractive target, and favourably affects CVD risk factors. The Diabetes Prevention Program and the Finnish Diabetes Prevention studies showed that changes in lifestyle prevented or delayed the onset of new cases of T2DM in subjects with pre-diabetes by 58%. However, a fraction of participants still developed T2DM, suggesting a residual risk. Moreover, lifestyle changes are not usually followed on a long-term basis as shown in EUROASPIRE with an increase in new onset T2DM by 60% in subjects with CVD in just over a decade. T2DM is characterized by insulin resistance and/or β-cell dysfunction (impaired insulin secretion). Various interventions targeting those two mechanisms (e.g. metformin, thiazolidinediones, acarbose, orlistate, bariatric surgery, renin-angiotensin-aldosterone system axis inhibitors, fibrates, incretin mimetics or enhancers) can prevent or delay T2DM. Widespread application of these measures has, however, been limited by financial considerations, even though cost-effectiveness might be achieved at the population level. This review will investigate feasibility and usefulness of T2DM prevention, further to that achieved with lifestyle changes, in a cost-effective manner.