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?
OBJECTIVE
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 2 kcal/min on glucose homeostasis were examined in patients with Type 2 diabetes.


METHODS
A total of 10 people with Type 2 diabetes were studied on two different days, 30 min after oral ingestion of sitagliptin (100 mg) or placebo. Intraduodenal glucose was infused at 2 kcal/min (60 g over 120 min), 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.


RESULTS
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).


CONCLUSIONS
Sitagliptin increased the heart rate response to intraduodenal glucose infusion at 2 kcal/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.
Discipline of Medicine, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
T
T
Wu
L G
LG
Trahair
M J
MJ
Bound
C F
CF
Deacon
M
M
Horowitz
C K
CK
Rayner
K L
KL
Jones
D000284:Administration, Oral; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D012189:Retrospective Studies; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D005749:Gastric Inhibitory Polypeptide; D005947:Glucose; D000068900:Sitagliptin Phosphate