A Dipeptidyl Peptidase–4 Inhibitor, Des-Fluoro-Sitagliptin, Improves Endothelial Function and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E–Deficient Mice

Study Questions:

What is the effect of dipeptidyl peptidase-4 (DPP-4) inhibition on endothelial function and atherosclerosis in mice?


Endothelial function and atherosclerosis were measured in apolipoprotein E–deficient mice fed a high-fat diet with or without des-fluoro-sitagliptin (DFS).


Mice fed DFS showed improved endothelial function and reduced atherosclerosis. In vitro studies demonstrated that DFS enhanced glucagon-like peptide (GLP)-1 effects on cellular signaling pathways leading to reduced proinflammatory cytokine production in reponse to lipopolysaccharide (LPS).


The authors concluded that the DPP-4 inhibitor, DFS, exhibited antiatherogenic effects by augmenting GLP-1 activity in macrophages and endothelium.


Improved therapies are needed to reduce the cardiovascular risk associated with diabetes since glucose control alone does not appear to be adequate. In addition to antihyperglycemic activities, DPP-4 inhibitors may have beneficial pleiotropic effects on vascular disease processes. This study adds to other preclinical studies by demonstrating that atherosclerosis is reduced and endothelial function is preserved in hyperlipidemic mice treated with DFS. This class of drugs may be useful in both treating hyperglycemia and reducing the vascular risk associated with type 2 diabetes.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Heart Failure and Cardiac Biomarkers, Diet

Keywords: Hyperglycemia, Dipeptidyl Peptidase 4, Atherosclerosis, Lipopolysaccharides, Enzyme Inhibitors, Risk Factors, Pyrazines, Endothelium, Glucagon-Like Peptides, Cardiology, Cardiovascular Diseases, Hypoglycemic Agents, Diet, Diabetes Mellitus, Triazoles

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