Time course and mechanisms of the anti‐hypertensive and renal effects of liraglutide treatment

Aims 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 –pro ANP ) 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 –pro ANP 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.