Effects of exenatide on postprandial vascular endothelial dysfunction in type 2 diabetes mellitus

BACKGROUND: Basic studies have shown that glucagon-like peptide-1 (GLP-1) analogs exert a direct protective effect on the vascular endothelium in addition to their indirect effects on postprandial glucose and lipid metabolism. GLP-1 analogs are also reported to inhibit postprandial vascular endothelial dysfunction. This study examined whether the GLP-1 analog exenatide inhibits postprandial vascular endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). METHODS: Seventeen patients with T2DM underwent a meal tolerance test to examine changes in postprandial vascular endothelial function and in glucose and lipid metabolism, both without exenatide (baseline) and after a single subcutaneous injection of 10 μg exenatide. Vascular endothelial function was determined using reactive hyperemia index (RHI) measured by peripheral arterial tonometry before and 120 min after the meal loading test. The primary endpoint was the difference in changes in postprandial vascular endothelial function between the baseline and exenatide tests. RESULTS: The natural logarithmically-scaled RHI (L_RHI) was significantly lower after the baseline meal test but not in the exenatide test. The use of exenatide resulted in a significant decrease in triglycerides (TG) area under the curve and coefficient of variation (CV). The change in L_RHI correlated with changes in CV of triglycerides and HDL-cholesterol. Multivariate analysis identified changes in triglyceride CV as the only determinant of changes in L_RHI, contributing to 41% of the observed change. CONCLUSIONS: Exenatide inhibited postprandial vascular endothelial dysfunction after the meal loading test, suggesting that exenatide has a multiphasic anti-atherogenic action involving not only glucose but also lipid metabolism. TRIAL REGISTRATION: ClinicalTrials.gov: UMIN000015699.