Type 2 diabetes mellitus (DM) is constantly increasing worldwide and its most critical determinant of morbidity and mortality is still represented by cardiovascular (CV) complications. For years, cardiologists' approach to diabetic patients has been focused on risk factors optimization, with positive results. However, the management of DM per se was never truly considered in order to obtain prevention from major CV events, because medications used for glycemic control were not expected to gain CV benefit. Early trials concerning intensive versus conventional glycemia control did not prove useful in reducing the number of CV events. The introduction of new molecules led to a game change in DM treatment, as some new glucose-lowering drugs (GLDs), such as sodium-glucose linked transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), showed not only to be safe but also to ensure CV benefit. A combination of anti-atherogenic effects and hemodynamic improvements are likely explanations of the observed reduction of CV events and mortality. These evidence opened a completely new era in the field of GLDs and of DM treatment. Nonetheless, the presence of residual cardiovascular risk despite optimal medical therapy remains an issue and an aggressive strategy against multiple risk factors is suggested. A paradigm shift toward a new approach to DM management should be made with no further delay with the use of medications that may prevent CV events in an integrated strategy of CV risk reduction.
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