Effects of sitagliptin on blood pressure and heart rate in response to intraduodenal glucose infusion in patients with Type 2 diabetes: a potential role for glucose-dependent insulinotropic polypeptide?

Abstract

To evaluate the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin on blood pressure and heart rate, measured during a previously reported study, in which the effects of sitagliptin during intraduodenal glucose infusion at the rate of 2kcal/min on glucose homeostasis were examined in patients with Type 2 diabetes. A total of 10 people with Type 2 diabetes were studied on two different days, 30min after oral ingestion of sitagliptin (100mg) or placebo. Intraduodenal glucose was infused at 2kcal/min (60g over 120min), and blood pressure, heart rate, plasma glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (total and intact), glucose, insulin and glucagon responses were evaluated. In response to intraduodenal glucose infusion, heart rate (treatment effect: P=0.001) and serum insulin concentration (treatment × time interaction: P=0.041) were higher after sitagliptin treatment than placebo, without a significant difference in blood pressure, plasma glucagon or glucose. During intraduodenal glucose infusion, there was a substantial increase in plasma total glucose-dependent insulinotropic polypeptide on both days (time effect: P<0.001), but not in total glucagon-like peptide-1. After sitagliptin, plasma intact glucagon-like peptide-1 concentration increased slightly (treatment×time interaction: P=0.044) and glucose-dependent insulinotropic polypeptide concentration increased substantially (treatment × time interaction: P=0.003).The heart rate response to intraduodenal glucose was related directly to plasma intact glucose-dependent insulinotropic polypeptide concentrations (r=0.75, P=0.008). Sitagliptin increased the heart rate response to intraduodenal glucose infusion at 2kcal/min in people with Type 2 diabetes, which was associated with augmentation of plasma intact glucose-dependent insulinotropic polypeptide concentrations. These observations warrant further clarification of a potential role for glucose-dependent insulinotropic polypeptide in the control of the 'gut-heart' axis.