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

Cardiovascular Safety

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Jennifer B. Green, MD

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Postgraduate Medicine:

Volume 124 No. 4


Clinical Focus

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DOI: 10.3810/pgm.2012.07.2566
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