Background: Despite substantial improvements over the years, diabetes mellitus is still
associated with cardiovascular disease, heart failure, and excess mortality.
Objective: The objective of this article is to examine existing data on the reduction of cardiovascular
morbidity and mortality in diabetes. Control of glycemia, lipid levels, and blood pressure are described
in brief. The main scope of this article is, however, to review the glucose-independent cardiovascular
effect of antidiabetic pharmacological agents (mainly other than insulin).
Methods: The article is a narrative review based on recently published reviews and meta-analyses
complemented with data from individual trials, when relevant.
Results and Discussion: Older data suggest a cardioprotective role of metformin (an inexpensive
and safe drug); a role to date not convincingly challenged. The cardiovascular effects of thiazolidinediones,
sulphonylurea, and glinides are debatable. Recent large-scale cardiovascular outcome
trials suggest a neutral profile of dipeptidyl peptidase 4 inhibitors, yet provide compelling evidence
of cardioprotective effects of glucagon-like 1 receptor antagonists and sodium-glucose transporter
Conclusion: Metformin may have a role in primary and secondary prevention of cardiovascular disease;
glucagon-like 1 receptor antagonists and sodium-glucose co-transporter 2 inhibitors play a
role in secondary prevention of atherosclerotic cardiovascular disease. Sodium-glucose transporter
2 inhibitors have a role to play in both primary and secondary prevention of heart failure; yet, they
carry a small risk of the potentially dangerous adverse effect, euglycemic diabetic ketoacidosis.