The risk of cardiovascular disease (CVD) (myocardial infarction, stroke, peripheral vascular disease) is twice in type 2 diabetes (T2D) patients compared to non-diabetic subjects. Furthermore, cardiovascular disease (CV) is the leading cause of death in patients with T2D.In the last years several clinical intervention studies with new anti-hyperglycaemic drugs have been published, and they have shown a positive effect on the reduction of mortality and cardiovascular risk in T2D patients. In particular, these studies evaluated sodium/glucose-2 cotransporter inhibitors (SGLT2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RA).In secondary prevention, it was clearly demonstrated that SGLT2i and GLP-1RA drugs reduce CV events and mortality, and new guidelines consider now these drugs as first choice (after metformin) in the treatment of T2D; there are also some signs that they may be effective also in primary prevention of CVD. However, the mechanisms involved in cardiovascular protection are not yet fully understood, but they appear to be both "glycaemic" and "extra-glycaemic".In this review, we will examine the fundamental results of the clinical trials on SGLT2i and GLP-1RA, their clinical relevance in term of treatment of T2D, and we will discuss the mechanisms that may explain how these drugs exert their cardiovascular protective effects.
Keywords: CVD outcome trials; Cardiovascular disease (CVD); Heart failure; Ketogenesis; MACE; Primary prevention; Real-world trials; Sodium/Hydrogen Exchanger (NHE); Tubuloglomerular feedback.