Cardiovascular (CV) disease is the most common cause of mortality in patients with type2 diabetes (T2DM). In recent years, several glucose-lowering drugs from two therapeutic families, GLP-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter type 2 inhibitors (SGLT-2i), have shown a reduction in CV morbidity and mortality in patients with T2DM and high CV risk. SGLT-2i, unlike GLP-1 RAs, also reduce the risk of hospital admission due to heart failure. Both therapeutic groups reduce the progression of diabetic kidney disease (DKD). The cardioprotective mechanism of SGLT-2i appears to be predominantly haemodynamic and shows an early onset, while that of GLP-1 RAs is mostly anti-atherosclerotic with a slow and progressive onset. At present, several scientific societies recommend the preferential use of GLP-1 RAs and SGLT-2i, with demonstrated CV benefit in patients with T2DM and cardiovascular disease or DKD.