title: Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovshin
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Annette
authors.initials: A
authors.lastname: Barnie
authors.affiliation: Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ariana
authors.initials: A
authors.lastname: DeAlmeida
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Logan
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada drucker@lunenfeld.ca.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Drucker
mesh_terms: D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000067757:Glucagon-Like Peptide-1 Receptor; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009765:Obesity; D010446:Peptide Fragments / Q000097:blood; D018027:Receptors, Glucagon / Q000819:agonists / Q000097:blood; D012964:Sodium / Q000652:urine
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000069450:Liraglutide; D009320:Atrial Natriuretic Factor; D052216:Glucagon-Like Peptide 1; D012964:Sodium