Cardiovascular Safety and Benefits of Non-Insulin Antihyperglycemic Drugs for the Treatment of Type 2 Diabetes Mellitus - Part 1.

Cardiovascular disease (CVD) is a major contributor to the morbidity and mortality associated with type 2 diabetes mellitus (T2DM). With T2DM growing in pandemic proportions, there will be profound healthcare implications of CVD in person with diabetes. The ideal drugs to improve outcomes in T2DM are those having antiglycemic efficacy in addition to cardiovascular (CV) safety, which has to be determined in appropriately designed CV outcome trials as mandated by regulatory agencies. Available evidence is largely supportive of metformin's CV safety and potential CVD risk reduction effects, whereas sulfonylureas are either CV risk neutral or are associated with variable CVD risk. Pioglitazone was also associated with improved CVD risk in patients with diabetes. The more recent antihyperglycemic medications have shown promise with regards to CVD risk reduction in T2DM patients at a high CV risk. Glucagon-like peptide-1 receptor agonists, a type of incretin-based therapy, were associated with better CV outcomes and mortality in T2DM patients, leading to the Food and Drug Administration approval of liraglutide to reduce CVD risk in high-risk T2DM patients. Ongoing and planned randomized controlled trials of the newer drugs should clarify the possibility of class effects, and of CVD risk reduction benefits in low-moderate CV risk patients. While metformin remains the first-line antiglycemic therapy in T2DM, glucagon-like peptide-1 receptor agonists should be appropriately prescribed in T2DM patients with baseline CVD or in those at a high CVD risk to improve CV outcomes. Dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter-2 inhibitors are discussed in the second part of this review.