title: Time course and mechanisms of the anti-hypertensive and renal effects of liraglutide treatment.
abstract: OBJECTIVE
  Glucagon-like peptide-1 receptor agonist studies have revealed clinically significant reductions in systolic blood pressure (SBP). The aim was to investigate the time course of the anti-hypertensive effect of liraglutide treatment and potential underlying mechanisms.
  
  
  METHODS
  We used an open-label, single-centre trial; 31 participants with Type 2 diabetes and hypertension completed the study. All participants were treated with liraglutide escalated to a maximum dose of 1.8 mg/day for 7 weeks, followed by a 21-day washout period. The primary outcome was a change in 24-h SBP.
  
  
  RESULTS
  Twenty-four-h SBP increased by 10 mmHg on day 3 (P = 0.008) and 7 mmHg on day 7 (P = 0.033, 0.6 mg/day). On day 29, (1.8 mg/day), 24-h SBP was 7 mmHg lower compared with baseline (P = 0.11). Following the treatment period (day 49) and after washout (day 70), 24-h BP was equivalent to baseline. In addition, extracellular volume (ECV) was reduced by 2.0 l [95% confidence interval (CI) = 1.0-3.1 l, P < 0.001] and midregional-pro-atrial natriuretic peptide (MR-proANP) was reduced by 20% (95% CI = 12-28%, P < 0.001). Also, urinary albumin excretion declined by 30% (95% CI = 12-44%, P = 0.003), GFR by 11 ml/min/1.73 m(2) (95% CI = 7.2-14.4 ml/min/1.73 m(2) , P < 0.001) and fractional albumin excretion by 29% (95% CI = 3-48%, P = 0.032).
  
  
  CONCLUSIONS
  Liraglutide treatment was associated with an initial increase in 24-h SBP, followed by a 7 mmHg reduction after escalation to 1.8 mg/day. This effect subsided after 4 weeks of maximum dose. Reductions in ECV and MR-proANP may explain the anti-hypertensive potential. Liraglutide treatment was associated with reversible reductions in albuminuria and GFR, which has to be confirmed in randomized trials.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: B J
authors.initials: BJ
authors.lastname: von Scholten
authors.forename: M
authors.initials: M
authors.lastname: Lajer
authors.forename: J P
authors.initials: JP
authors.lastname: Goetze
authors.forename: F
authors.initials: F
authors.lastname: Persson
authors.forename: P
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000652:urine; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015994:Incidence; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D000069450:Liraglutide / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists