Treatment of diabetes mellitus has borne much fruit in the prevention of cardiovascular disease.

Cardiovascular (CV) disease is the most alarming complication of diabetes mellitus (DM), and a strategy aiming at cardiovascular event prevention in diabetes mellitus has long been debated. Large landmark clinical trials have shown cardiovascular benefits of intensive glycemic control as a 'legacy effect' in newly diagnosed type 2 diabetes mellitus. In contrast, we have learned that excessive intervention aimed at strong glycemic control could cause unexpected cardiovascular death in patients who are resistant to treatments against hyperglycemia. It has also been shown that the comprehensive multifactorial intervention for cardiovascular risk factors that was advocated in the current guideline provided substantial cardiovascular event reduction. The impact of classical antidiabetic agents launched before 1990s on cardiovascular events is controversial. Although there are many clinical or observational studies assessing the impact of those agents on cardiovascular events, the conclusions are inconsistent owing to variable patient backgrounds and concomitant antidiabetic agents among the studies. Moreover, most of them were not large-scale, randomized, cardiovascular outcome trials. In contrast, GLP-1RA (glucagon-like peptide-1 receptor agonist) and SGLT2 (sodium-glucose cotransporter 2) inhibitors have demonstrated undeniable cardiovascular benefits in large-scale, randomized, controlled trials. Whereas GLP-1RAs decrease atherosclerotic disease, especially stroke, SGLT2 inhibitors mainly prevent heart failure. SGLT2 inhibitors are superior to GLP-1RAs with respect to hard renal outcomes. Therefore, it can be said that drugs such as GLP-1RAs and SGLT2 inhibitors that prevent cardiovascular events, in addition to their glucose-lowering effect, are incredible novel tools that we have gained for use in diabetic treatment.