The dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus: cardiovascular safety.
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.
Division of Endocrinology, Duke University Medical Center, Durham, NC 27705, USA. green094@mc.duke.edu
Jennifer B
JB
Green
D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002319:Cardiovascular System / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D015201:Meta-Analysis as Topic
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins