Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus

Hypertension. 2014 Oct;64(4):731-7. doi: 10.1161/HYPERTENSIONAHA.114.03062. Epub 2014 Jun 30.

Abstract

Glucagon-like peptide-1 receptor agonists, used to treat type 2 diabetes mellitus, are associated with small reductions in systolic blood pressure (SBP) and increases in heart rate. However, findings based on clinic measurements do not adequately assess a drug's 24-hour pharmacodynamic profile. The effects of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, on BP and heart rate were investigated using ambulatory BP monitoring. Patients (n=755; 56±10 years; 81% white; 48% women), with type 2 diabetes mellitus, taking ≥1 oral antihyperglycemic medication, with a clinic BP between 90/60 and 140/90 mm Hg were randomized to dulaglutide (1.5 or 0.75 mg) or placebo subcutaneously for 26 weeks. Ambulatory BP monitoring was performed at baseline and at 4, 16, and 26 weeks. The primary end point was change from baseline to week 16 in mean 24-hour SBP, a tree gatekeeping strategy compared the effects of dulaglutide to placebo. Both doses of dulaglutide were noninferior to placebo for changes in 24-hour SBP and diastolic blood pressure, and dulaglutide 1.5 mg significantly reduced SBP (least squares mean difference [95% confidence interval]), -2.8 mm Hg [-4.6, -1.0]; P≤0.001). Dulaglutide 0.75 mg was noninferior to placebo (1.6 bpm; [0.3, 2.9]; P≤0.02) for 24-hour heart rate (least squares mean difference [95% confidence interval]), but dulaglutide 1.5 mg was not (2.8 bpm [1.5, 4.2]). Dulaglutide 1.5 mg was associated with a reduction in 24-hour SBP and an increase in 24-hour heart rate. The mechanisms responsible for the observed effects remain to be clarified.

Keywords: blood pressure; blood pressure monitoring, ambulatory; dulaglutide; glucagon-like peptide-1; heart rate; hypertension; type 2 diabetes mellitus.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Blood Pressure Monitoring, Ambulatory
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diarrhea / chemically induced
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides / adverse effects
  • Glucagon-Like Peptides / analogs & derivatives*
  • Glucagon-Like Peptides / therapeutic use
  • Glycated Hemoglobin A / metabolism
  • Heart Rate / drug effects*
  • Heart Rate / physiology
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Immunoglobulin Fc Fragments / adverse effects
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Receptors, Glucagon / agonists*
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Treatment Outcome
  • Vomiting / chemically induced

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Receptors, Glucagon
  • Recombinant Fusion Proteins
  • Glucagon-Like Peptides
  • dulaglutide