Abstract 13632: Antidiabetic Monotherapy by Linagliptin Provides Multiple Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics With Coronary Artery Disease
Background: Diabetes mellitus is thought to be highly involved in complex atherothrombogenic processes, but the antiatherosclerotic therapies in patients with type-2 diabetes mellitus have not been established.
We assessed hypothesis antidiabetic monotherapy with linagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4-I) recently developed antidiabetic agent, pleiotropically inhibits atherosclerotic progression in patients with type-2 diabetes mellitus.
Methods: Type-2 diabetic patients with stable coronary artery disease were randomized to group-L where they received antidiabetic monotherapy with linagliptin, or to group-C where they continued therapy without a DPP4-I.
We quantified flow-mediated endothelium-dependent dilatation of brachial artery after 5 minutes forearm occlusion (FMD), and dilatation of brachial artery after sublingual administration of nitroglycerin (TNG) using high-resolution ultrasonography, and we also quantified brachial-to-ankle pulse wave velocity (PWV).
Changes in FMD, TNG, PWV, and other clinical variables were compared between the two study groups.
Results: All the patients in group-L (n=12) manifested good compliance to the treatment and improvements in diabetic and lipid variables represented by HbA1c and LDL, while those in group-C (n=12) showed no improvement.
FMD (%) increased after medication in group-L (from 3.9±2.1 to 6.9±2.8, p<0.01), while it remained unchanged in group-C (from 4.1±2.0 to 4.0±2.3, p=0.80). TNG (%) remained unchanged in group-L (from 14.4±3.9 to 14.3±3.8, p=0.78) and in group-C (from 14.8±4.0 to 14.5±4.7, p=0.84).
PWV (cm/s) decreased in group-L (from 1725±214cm/s to 1673±234cm/s, p=0.03), but it did not change in group-C (from 1745±228cm/s to 1748±212cm/s, p=0.79).
Changes of FMD or PWV in group-L did not correlate to those of HbA1c (FMD: r=0.16, p=0.59, PWV: r=0.14, p=0.58).
Conclusion: These results indicate inhibition of dipeptidyl peptidase-4 with linagliptin alone in diabetic patients improves endothelial function, and reduces arterial wall stiffness independent of reversal for diabetic status, which may have novel potential benefits of linagliptin for management of progressive atherosclerosis in type-2 diabetics with coronary artery disease.
- © 2013 by American Heart Association, Inc.