Eli Lilly and Company, Indianapolis, USA.
Cardiovasc Diabetol. 2010 Jan 28;9:6. doi: 10.1186/1475-2840-9-6.
Cardiovascular effects of glucose-lowering agents are of increasing interest. Our aim was to assess the effects of the glucagon-like peptide-1 receptor agonist exenatide on heart rate (HR) and blood pressure (BP) in subjects with type 2 diabetes mellitus (T2DM).
In this double-blind, placebo-controlled trial, subjects with T2DM on metformin and/or a thiazolidinedione were randomized to receive exenatide (5 microg for 4 weeks followed by 10 microg) or placebo BID for 12 weeks. Heart rate and BP were assessed with 24-hour ambulatory BP monitoring. The primary measure was change from baseline in mean 24-hour HR.
Fifty-four subjects (28 exenatide, 26 placebo) were randomized and comprised the intent-to-treat population. Baseline values (exenatide and placebo) were (mean +/- SE) 74.4 +/- 2.1 and 74.5 +/- 1.9 beats/minute for HR, 126.4 +/- 3.2 and 119.9 +/- 2.8 mm Hg for systolic BP (SBP), and 75.2 +/- 2.1 and 70.5 +/- 2.0 mm Hg for diastolic BP (DBP). At 12 weeks, no significant change from baseline in 24-hour HR was observed with exenatide or placebo (LS mean +/- SE, 2.1 +/- 1.4 versus -0.7 +/- 1.4 beats/minute, respectively; between treatments, p = 0.16). Exenatide therapy was associated with trends toward lower 24-hour, daytime, and nighttime SBP; changes in DBP were similar between groups. No changes in daytime or nighttime rate pressure product were observed. With exenatide, body weight decreased from baseline by -1.8 +/- 0.4 kg (p < 0.0001; treatment difference -1.5 +/- 0.6 kg, p < 0.05). The most frequently reported adverse event with exenatide was mild to moderate nausea.
Exenatide demonstrated no clinically meaningful effects on HR over 12 weeks of treatment in subjects with T2DM. The observed trends toward lower SBP with exenatide warrant future investigation.
NCT00516074.
降糖药物对心血管的影响正受到越来越多的关注。我们旨在评估胰高血糖素样肽-1 受体激动剂 exenatide 对 2 型糖尿病（T2DM）患者心率（HR）和血压（BP）的影响。
在这项双盲、安慰剂对照试验中，接受二甲双胍和/或噻唑烷二酮治疗的 T2DM 患者被随机分为 exenatide（4 周时 5μg，然后是 10μg，bid）或安慰剂组，治疗 12 周。通过 24 小时动态血压监测评估心率和血压。主要测量指标是平均 24 小时 HR 从基线的变化。
54 名受试者（28 名 exenatide，26 名安慰剂）被随机分组，构成意向治疗人群。基线值（exenatide 和安慰剂）分别为（均值 +/- SE）74.4 +/- 2.1 和 74.5 +/- 1.9 次/分钟的 HR、126.4 +/- 3.2 和 119.9 +/- 2.8 mmHg 的收缩压（SBP）以及 75.2 +/- 2.1 和 70.5 +/- 2.0 mmHg 的舒张压（DBP）。在 12 周时，exenatide 或安慰剂治疗与基线相比，24 小时 HR 无明显变化（LS 均值 +/- SE，分别为 2.1 +/- 1.4 与 -0.7 +/- 1.4 次/分钟；治疗间差异，p = 0.16）。exenatide 治疗与 24 小时、白天和夜间 SBP 呈下降趋势相关；两组之间 DBP 的变化相似。白天或夜间心率血压乘积无变化。用 exenatide 治疗，体重从基线下降了-1.8 +/- 0.4 kg（p < 0.0001；治疗差异 -1.5 +/- 0.6 kg，p < 0.05）。exenatide 最常见的不良反应是轻度至中度恶心。
在 12 周的治疗中，exenatide 对 T2DM 患者的 HR 没有显示出有临床意义的影响。exenatide 观察到的 SBP 下降趋势值得进一步研究。
NCT00516074。
