von Scholten B J, Lajer M, Goetze J P, Persson F, Rossing P
Steno Diabetes Center, Gentofte, Denmark.
Diabet Med. 2015 Mar;32(3):343-52. doi: 10.1111/dme.12594. Epub 2014 Oct 15.
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.
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.
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).
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.
胰高血糖素样肽-1受体激动剂研究显示收缩压（SBP）有临床显著降低。本研究旨在探讨利拉鲁肽治疗的降压作用时间过程及潜在机制。
我们采用开放标签、单中心试验；31例2型糖尿病合并高血压患者完成了研究。所有参与者均接受利拉鲁肽治疗，剂量逐渐增加至最大剂量1.8mg/天，持续7周，随后为21天的洗脱期。主要结局是24小时SBP的变化。
第3天24小时SBP升高10mmHg（P = 0.008），第7天升高7mmHg（P = 0.033，0.6mg/天）。第29天（1.8mg/天），24小时SBP较基线降低7mmHg（P = 0.11）。治疗期（第49天）和洗脱期后（第70天），24小时血压与基线相当。此外，细胞外液量（ECV）减少2.0L[95%置信区间（CI）=1.0 - 3.1L，P < 0.001]，中段心房利钠肽前体（MR-proANP）降低20%（95%CI = 12 - 28%，P < 0.001）。同时，尿白蛋白排泄量下降30%（95%CI = 12 - 44%，P = 0.003），肾小球滤过率（GFR）下降11ml/min/1.73m²（95%CI = 7.2 - 14.4ml/min/1.73m²，P < 0.001），白蛋白排泄分数下降29%（95%CI = 3 - 48%，P = 0.032）。
利拉鲁肽治疗初期24小时SBP升高，剂量增至1.8mg/天后降低7mmHg。最大剂量4周后该效应消退。ECV和MR-proANP的降低可能解释了其降压潜力。利拉鲁肽治疗与蛋白尿和GFR的可逆性降低有关，这有待在随机试验中证实。
