Effect of a 3-Week Treatment with GLP-1 Receptor Agonists on Vasoactive Hormones in Euvolemic Participants.

Abstract

CONTEXT:

Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) exert cardiovascular benefits by reducing plasma glucose, body weight, and blood pressure. The blood pressure-lowering effect may be mediated by angiotensin II (ANG II) suppression and consecutive natriuresis. However, the role of ANG II and other vasoactive hormones on GLP-1 RA treatment has not been clearly defined.

OBJECTIVE:

This work aimed to investigate the effect of a 3-week treatment with the GLP-1 RA dulaglutide on vasoactive hormones, that is, renin, ANG II, aldosterone, mid-regional proatrial natriuretic peptide (MP-proANP), and natriuresis in euvolemic participants.

METHODS:

Randomized, double-blinded, placebo-controlled, crossover trials were conducted at University Hospital Basel, Switzerland. A total of 54 euvolemic participants, including 20 healthy individuals and 34 patients with primary polydipsia, received a subcutaneous injection of dulaglutide (Trulicity) 1.5 mg and placebo (0.9% sodium chloride) once weekly over a 3-week treatment phase.

RESULTS:

After a 3-week treatment phase, dulaglutide showed no effect on plasma renin, plasma ANG II, or plasma aldosterone levels in comparison to placebo. Natriuresis remained unchanged or decreased on dulaglutide depending on the measured parameter. Dulaglutide significantly decreased plasma MR-proANP levels (treatment effect: 10.60 pmol/L; 95% CI, -14.70 to -7.90; P < .001) and systolic blood pressure (median: 3 mm Hg; 95% CI, -5 to 0; P = .036), whereas heart rate increased (median: 5 bpm; 95% CI, 3-11; P < .001).

CONCLUSION:

In euvolemic participants, a 3-week treatment of dulaglutide reduced systolic blood pressure independently of plasma renin, ANG II, or aldosterone levels and urinary sodium excretion. The reduction in MR-proANP might be secondary to reduced arterial pulse pressure.

• Authors: Tanja Vukajlovic, Clara O Sailer, Ali Asmar, Boye L Jensen, Deborah R Vogt, Mirjam Christ-Crain, Bettina Winzeler
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 107 Issue 6 Pg. e2581-e2589 (05 17 2022) ISSN: 1945-7197 [Electronic] United States
• PMID: 35134170 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Immunoglobulin Fc Fragments
• Recombinant Fusion Proteins
• Angiotensin II
• Aldosterone
• Glucagon-Like Peptide 1
• Renin

Topics

• Aldosterone (pharmacology)
• Angiotensin II
• Diabetes Mellitus, Type 2
• Double-Blind Method
• Glucagon-Like Peptide 1 (pharmacology)
• Glucagon-Like Peptide-1 Receptor (agonists)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Immunoglobulin Fc Fragments
• Natriuresis
• Recombinant Fusion Proteins (pharmacology, therapeutic use)
• Renin