Cardiovascular Effects of Hypoglycemic Agents in Diabetes Mellitus

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 2 inhibitors. 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.