TY - JOUR

T1 - Time course and mechanisms of the anti-hypertensive and renal effects of liraglutide treatment

AU - von Scholten, B. J.

AU - Lajer, M.

AU - Goetze, J. P.

AU - Persson, F.

AU - Rossing, P.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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-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 m2 (95% CI = 7.2-14.4 ml/min/1.73 m2, 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. What's new?: We are the first to have investigated the effect of treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on 24-h blood pressure and 24-h heart rate, in people with Type 2 diabetes and hypertension. Initially, both blood pressure and heart rate increased, but subsequently blood pressure returned to the baseline level. Reductions in extracellular volume and plasma midregional-pro-atrial natriuretic peptide may explain the anti-hypertensive potential of GLP-1 treatment. We are the first to have investigated the effect of liraglutide treatment on accurately measured GFR, 24-h urinary albumin excretion and fractional albumin excretion, and found treatment to be associated with significant and reversible reductions. Our novel findings will have an important impact on the expanding field of GLP-1 treatment, but they need to be confirmed in randomized blinded trials.

AB - 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-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 m2 (95% CI = 7.2-14.4 ml/min/1.73 m2, 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. What's new?: We are the first to have investigated the effect of treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on 24-h blood pressure and 24-h heart rate, in people with Type 2 diabetes and hypertension. Initially, both blood pressure and heart rate increased, but subsequently blood pressure returned to the baseline level. Reductions in extracellular volume and plasma midregional-pro-atrial natriuretic peptide may explain the anti-hypertensive potential of GLP-1 treatment. We are the first to have investigated the effect of liraglutide treatment on accurately measured GFR, 24-h urinary albumin excretion and fractional albumin excretion, and found treatment to be associated with significant and reversible reductions. Our novel findings will have an important impact on the expanding field of GLP-1 treatment, but they need to be confirmed in randomized blinded trials.

UR - http://www.scopus.com/inward/record.url?scp=84922572669&partnerID=8YFLogxK

U2 - 10.1111/dme.12594

DO - 10.1111/dme.12594

M3 - Journal article

C2 - 25251901

AN - SCOPUS:84922572669

VL - 32

SP - 343

EP - 352

JO - Diabetic Medicine Online

JF - Diabetic Medicine Online

SN - 1464-5491

IS - 3

ER -