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Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes.

AbstractOBJECTIVE:
GLP-1 receptor (GLP-1R) agonists induce natriuresis and reduce blood pressure (BP) through incompletely understood mechanisms. We examined the effects of acute and 21-day administration of liraglutide on plasma atrial natriuretic peptide (ANP), urinary sodium excretion, office and 24-h BP, and heart rate (HR).
RESEARCH DESIGN AND METHODS:
Liraglutide or placebo was administered for 3 weeks to hypertensive subjects with type 2 diabetes in a double-blinded, randomized, placebo-controlled crossover clinical trial in the ambulatory setting. End points included within-subject change from baseline in plasma ANP, Nt-proBNP, office BP, and HR at baseline and over 4 h following a single dose of liraglutide (0.6 mg) and after 21 days of liraglutide (titrated to 1.8 mg) versus placebo administration. Simultaneous 24-h ambulatory BP and HR monitoring and 24-h urine collections were measured at baseline and following 21 days of treatment.
RESULTS:
Plasma ANP levels did not change significantly after acute (+16.72 pg/mL, P = 0.24, 95% CI [-12.1, +45.5] at 2 h) or chronic (-17.42 pg/mL, 95% CI [-36.0, +1.21] at 2 h) liraglutide administration. Liraglutide significantly increased 24-h and nighttime urinary sodium excretion; however, 24-h systolic BP was not significantly different. Small but significant increases in 24-h and nighttime diastolic BP and HR were observed with liraglutide. Body weight, HbA1c, and cholesterol were lower, and office-measured HR was transiently increased (for up to 4 h) with liraglutide administration.
CONCLUSIONS:
Sustained liraglutide administration for 3 weeks increases urinary sodium excretion independent of changes in ANP or BP in overweight and obese hypertensive patients with type 2 diabetes.
AuthorsJulie A Lovshin, Annette Barnie, Ariana DeAlmeida, Alexander Logan, Bernard Zinman, Daniel J Drucker
JournalDiabetes care (Diabetes Care) Vol. 38 Issue 1 Pg. 132-9 (Jan 2015) ISSN: 1935-5548 [Electronic] United States
PMID25414155 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Chemical References
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Receptors, Glucagon
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Liraglutide
  • Atrial Natriuretic Factor
  • Glucagon-Like Peptide 1
  • Sodium
Topics
  • Adult
  • Aged
  • Atrial Natriuretic Factor (blood)
  • Blood Pressure (drug effects)
  • Body Weight
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 (drug therapy)
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Glucagon-Like Peptide 1 (administration & dosage, analogs & derivatives)
  • Glucagon-Like Peptide-1 Receptor
  • Heart Rate (drug effects)
  • Humans
  • Hypertension (drug therapy)
  • Liraglutide
  • Male
  • Middle Aged
  • Natriuresis (drug effects)
  • Natriuretic Peptide, Brain (blood)
  • Obesity
  • Peptide Fragments (blood)
  • Receptors, Glucagon (agonists, blood)
  • Sodium (urine)

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