The effects of GLP-1 based therapies on postprandial haemodynamics: Two randomised, placebo-controlled trials in overweight type 2 diabetes patients.

Abstract

AIMS:

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; HbA1c 7.3±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: Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Trynke Hoekstra, Mark H H Kramer, Michaela Diamant, Daniël H van Raalte
• Journal: Diabetes research and clinical practice (Diabetes Res Clin Pract) Vol. 124 Pg. 1-10 (Feb 2017) ISSN: 1872-8227 [Electronic] Ireland
• PMID: 28086201 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Hypoglycemic Agents
• Peptides
• Placebos
• Venoms
• Liraglutide
• Glucagon-Like Peptide 1
• Exenatide
• Sitagliptin Phosphate

Topics

• Adult
• Aged
• Blood Pressure (drug effects)
• Diabetes Mellitus, Type 2 (blood, drug therapy, physiopathology)
• Dipeptidyl-Peptidase IV Inhibitors (therapeutic use)
• Double-Blind Method
• Exenatide
• Fasting (blood)
• Female
• Glucagon-Like Peptide 1 (metabolism)
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Humans
• Hypoglycemic Agents (administration & dosage)
• Liraglutide (therapeutic use)
• Male
• Middle Aged
• Overweight (blood, complications, drug therapy, physiopathology)
• Peptides (therapeutic use)
• Placebos
• Postprandial Period (drug effects, physiology)
• Sitagliptin Phosphate (therapeutic use)
• Vascular Resistance (drug effects)
• Venoms (therapeutic use)