The Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Mellitus: Cardiovascular Safety

Abstract

The dipeptidyl peptidase–4 (DPP–4) inhibitors are a relatively new class of oral antidiabetic agents that improve glycemic control in patients with type 2 diabetes mellitus. These agents differ in structure, but all act by inhibiting the DPP–4 enzyme. Dipeptidyl peptidase–4 inhibition increases levels of the incretin hormones glucagon–like peptide–1 and glucose–dependent insulinotropic peptide, which in turn stimulate insulin secretion in a glucose–dependent fashion. Clinical trials have shown that DPP–4 inhibitors provide significant reductions in glycated hemoglobin levels, with a low risk of hypoglycemia. Animal model experiments and proof–of–concept studies suggest that the incretins favorably affect the cardiovascular system; it is possible that these same effects may be conveyed by DPP–4 inhibitor therapy. Pooled and meta–analyses of DPP–4 inhibitor clinical trial data have shown no increase in major adverse cardiovascular events, and, in fact, suggest a potential cardiovascular benefit to such therapy. Long–term cardiovascular safety trials are currently underway to more fully define and understand the cardiovascular impact of DPP–4 therapy in patients with type 2 diabetes mellitus.

Keywords:

• alogliptin
• cardiovascular
• DPP-4 inhibitors
• linagliptin
• saxagliptin
• sitagliptin
• vildagliptin