Patients with
type 2 diabetes (T2DM) have a significantly higher risk of developing
cardiovascular disease (CVD)-namely
myocardial infarction,
heart failure, and
stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of
hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear. Although current
antidiabetic drugs are highly effective for the management of
hyperglycemia, most T2DM patients remain exposed to a substantial and concrete risk of CVD. Over the last decade many
glucose-lowering agents have been tested for their safety and efficacy in T2DM with CVD. Noteworthy, most of these studies failed to show a significant benefit in terms of CV morbidity and mortality, despite intensive
glycemic control. The recent trials
Empagliflozin Cardiovascular Outcome Event Trial in
Type 2 Diabetes Mellitus Patients-Removing Excess
Glucose (EMPA-REG OUTCOME); Trial to Evaluate Cardiovascular and Other Long-term Outcomes with
Semaglutide in Subjects with
Type 2 Diabetes (SUSTAIN-6);
Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER); and
Insulin Resistance Intervention After
Stroke (IRIS) have shed some light on this important clinical issue, thus showing a convincing effect of
empagliflozin,
liraglutide, and
pioglitazone on CVD outcomes. Here we provide a critical and updated overview of the main
glucose-lowering agents and their risk/benefit ratio for the prevention of CVD in patients with T2DM.