Heart rate acceleration with GLP-1 receptor agonists in type 2 diabetes patients: an acute and 12-week randomised, double-blind, placebo-controlled trial
- 1 January 2017
- journal article
- research article
- Published by Oxford University Press (OUP) in Acta Endocrinologica
- Vol. 176 (1), 77-86
- https://doi.org/10.1530/eje-16-0507
Abstract
Objective: To examine mechanisms underlying resting heart rate (RHR) increments of GLP-1 receptor agonists in type 2 diabetes patients. Design: Acute and 12-week randomised, placebo-controlled, double-blind, single-centre, parallel-group trial. Methods: In total, 57 type 2 diabetes patients (mean ± s.d. age: 62.8 ± 6.9 years; BMI: 31.8 ± 4.1 kg/m2; HbA1c: 7.3 ± 0.6%), treated with metformin and/or sulfonylureas, were included between July 2013 and August 2015. In the acute study, the GLP-1 receptor agonist exenatide (n = 29) or placebo (saline 0.9%; n = 28) was infused intravenously. Subsequently, patients were again randomised to receive the GLP-1 receptor agonist liraglutide (n = 19) or matching placebo (n = 17) for 12 weeks. RHR and blood pressure (BP) were measured by oscillometric technique, systemic haemodynamics by finger photoplethysmography, sympathetic nervous system (SNS) activity by heart rate variability and arterial stiffness by applanation tonometry. This trial was registered at ClinicalTrials.gov (Nbib1744236). Results: Exenatide-infusion increased RHR (mean ± s.e.m. +7.5 ± 0.9 BPM, P < 0.001), and systolic and diastolic BP (both P < 0.05), compared with placebo. Vascular resistance increased during exenatide-infusion, whereas stroke volume and arterial stiffness decreased (P < 0.05). SNS activity and cardiac output were unaffected. Twelve-week treatment with liraglutide increased RHR (+6.6 ± 2.1 BPM), while reducing systolic BP (−12.6 ± 4.7 mmHg) and stroke volume (all P < 0.01). Cardiac output, vascular resistance, arterial stiffness and SNS activity remained unchanged (all P > 0.05). Conclusions: RHR acceleration with acute and 12-week GLP-1 receptor agonist treatment in type 2 diabetes patients is not explained by changes in SNS activity, and our data argue against vasodilation. In line with pre-clinical data, direct sino-atrial stimulation may be involved.Keywords
This publication has 33 references indexed in Scilit:
- Exenatide acutely increases heart rate in parallel with augmented sympathetic nervous system activation in healthy overweight malesBritish Journal of Clinical Pharmacology, 2016
- Effects of GLP-1 Receptor Agonists on Heart Rate and the Autonomic Nervous System Using Holter Electrocardiography and Power Spectrum Analysis of Heart Rate VariabilityDiabetes Care, 2015
- Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta-analysisDiabetes Research and Clinical Practice, 2015
- Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label TrialDiabetes Care, 2015
- Cardiovascular Actions of Incretin-Based TherapiesCirculation Research, 2014
- Elevated resting heart rate, physical fitness and all-cause mortality: a 16-year follow-up in the Copenhagen Male StudyHeart, 2013
- Investigation of the haemodynamic effects of exenatide in healthy male subjectsBritish Journal of Clinical Pharmacology, 2012
- Resting heart rate: A modifiable prognostic indicator of cardiovascular risk and outcomes?Canadian Journal of Cardiology, 2008
- Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery diseaseEuropean Heart Journal, 2005
- Interactions of exendin-(9–39) with the effects of glucagon-like peptide-1-(7–36) amide and of exendin-4 on arterial blood pressure and heart rate in ratsRegulatory Peptides, 1996