Abstract 95: Glucagon Like Peptide-1 (GLP-1) Does Not Cause Vasodilation Even When Dipeptidyl Peptidase 4 (DPP4) is Inhibited

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Glucagon-like peptide 1 (GLP-1) causes direct vasodilation in animal models. Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in diabetic patients by preventing the degradation of GLP-1. The direct effect of GLP-1 in the human vasculature, and how it is altered by DPP4 inhibition, has not been reported. This study tested the hypothesis that intra-arterial infusion of GLP-1 causes dose-dependent vasodilation, and that DPP4 inhibition potentiates the forearm blood flow (FBF) response to GLP-1 by decreasing its degradation.

Eight healthy, non-obese (BMI<30 kg/m2) subjects, age 28-54 years old (3 female) participated in this double-blind, placebo-controlled crossover study. On study days separated by at least one week subjects received DPP4 inhibitor (sitagliptin 200 mg p.o.) or placebo, followed by infusion of GLP-1 in the brachial artery at graded doses (0.45-3.60 pmol/min) for 5 minutes per dose.

Sitagliptin significantly decreased plasma DPP4 activity (p<0.001 vs. placebo). Sitagliptin did not significantly affect baseline heart rate or baseline FBF. Baseline mean arterial pressure was significantly higher during sitagliptin than during placebo [87.13 ± 2.10 mmHg versus 84.75 ± 3.28 mmHg, p=0.037]. GLP-1 concentrations were significantly higher after sitagliptin (Left Figure; N=5). There was no effect of GLP-1 on FBF either in the presence or absence of sitagliptin. Moreover, there was no interactive effect of GLP-1 and sitagliptin on FBF (Right Figure).

GLP-1 does not cause vasodilation in healthy humans even when its degradation is inhibited. These data have implications for the cardiovascular effects of DPP4 inhibitors and GLP-1 receptor agonists.

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