Cardiovascular impact of drugs used in the treatment of diabetes

Abstract

The International Diabetes Federation predicts that by 2035 10% of the population of the world will have been diagnosed with diabetes, raising serious concerns over the resulting elevated morbidity and mortality as well as the impact on health care budgets. It is also well recognized that cardiovascular disease is the primary cause of the high morbidity and mortality associated with diabetes, raising the concern that appropriate drug therapy should not only correct metabolic dysfunction, but also protect the cardiovascular system from the effects of, in particular, the epigenetic changes that result from hyperglycaemia. A number of new classes of drugs for the treatment of diabetes have been introduced in the past decade, providing the opportunity to optimize treatment; however, comparative information of the cardiovascular benefits, or risks, of the newer drugs versus older therapies such as metformin is variable. This review, in addition to summarizing the cellular basis for the therapeutic action of these drugs, addresses the evidence for their cardiovascular benefits and risks. A particular focus is provided on metformin as it is the first choice drug for most patients with type 2 diabetes.

Keywords: cardiovascular disease; diabetes; endothelial dysfunction; hyperglycaemia; hypoglycaemia; insulin; insulin resistance; metformin; sulfonylureas; thiazolidinediones.

Figure 1.

Summary of important sites of action and side effects and cardiovascular actions of drugs used in the treatment of diabetes. DPP-4, dipeptidyl peptidase 4; eNOS, endothelial nitric oxide synthase; GI, gastrointestinal; GLP-1, glucagon-like peptide 1; SGLT2, sodium glucose cotransporter 2; TZD, thiazolidinedione.