title: The effects of GLP-1 based therapies on postprandial haemodynamics: Two randomised, placebo-controlled trials in overweight type 2 diabetes patients.
abstract: OBJECTIVE
  To assess the effects of glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors on postprandial haemodynamics.
  
  
  METHODS
  57 patients with type 2 diabetes (mean±SD age 62.8±6.9years; BMI 31.8±4.1kg/m2; HbA1c7.3±0.6%) were included in an acute (exenatide- or placebo-infusion) and 12-week (liraglutide, sitagliptin or placebo) randomised, placebo-controlled, double-blind trial. Systemic haemodynamics (oscillometric technique and finger photoplethysmography), vascular stiffness (tonometry), and sympathetic nervous system (SNS)-activity (heart rate variability) were determined in the fasting state and following a standardised mixed meal.
  
  
  RESULTS
  In both studies, postprandial blood pressure (BP) decreased during placebo-intervention. Compared with placebo, acute exenatide-infusion increased postprandial diastolic BP (6.7 [95%-confidence interval 3.6-9.9]mmHg, p<0.001) and vascular resistance (683.6 [438.5-928.8]dyn*s/cm5/1.73m2, p<0.001), while cardiac index decreased (0.6 [0.40.8]L/min/1.73m2; p<0.001). Systolic BP, augmentation index and SNS-activity were unaffected. Twelve-week liraglutide-treatment did not affect postprandial haemodynamics, while sitagliptin decreased diastolic BP (3.5 [0.0-6.9] mmHg; p=0.050), vascular resistance (309.9 [66.6-553.1]dyn*s/cm5/1.73m2; p=0.013) and cardiac index (0.3 [0.0-0.6]L/min/1.73m2; p=0.040), compared with placebo. Neither liraglutide nor sitagliptin affected SNS-activity or augmentation index. All treatments significantly lowered postprandial glucose levels.
  
  
  CONCLUSIONS
  Acute exenatide-infusion prevented the meal-induced decline in diastolic BP, although prolonged liraglutide intervention did not affect postprandial haemodynamics. The meal-induced drop in BP was augmented during sitagliptin-treatment.
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands. Electronic address: mm.smits1@vumc.nl.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Lennart
authors.initials: L
authors.lastname: Tonneijck
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Marcel H A
authors.initials: MH
authors.lastname: Muskiet
authors.affiliation: Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Trynke
authors.initials: T
authors.lastname: Hoekstra
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Mark H H
authors.initials: MH
authors.lastname: Kramer
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D000077270:Exenatide; D005215:Fasting / Q000097:blood; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000627:therapeutic use; D010919:Placebos; D019518:Postprandial Period / Q000187:drug effects* / Q000502:physiology; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects; D014688:Venoms / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010455:Peptides; D010919:Placebos; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000068900:Sitagliptin Phosphate
keywords: Exenatide; GLP-1 receptor agonist; Haemodynamics; Heart rate; Liraglutide; Sympathetic nervous system