Maggs David G, Fineman Mark, Kornstein Jonathan, Burrell Terrie, Schwartz Sherwyn, Wang Yan, Ruggles James A, Kolterman Orville G, Weyer Christian
Amylin Pharmaceuticals, Inc, San Diego, California 92121, USA.
Diabetes Metab Res Rev. 2004 Jan-Feb;20(1):55-60. doi: 10.1002/dmrr.419.
To assess the postprandial glucose-lowering effect of the human amylin analog pramlintide when given with insulin lispro in subjects with type 2 diabetes, with an emphasis on the optimal dose timing relative to meals.
In this randomized, single-blind, placebo-controlled, five-way crossover study, 19 subjects with type 2 diabetes using insulin lispro underwent five consecutive mixed-meal tests. In randomized order, subjects received subcutaneous injections of placebo at -15 min or 120-microg pramlintide at -15, 0, +15, or +30 min relative to the standardized breakfast after an overnight fast. Insulin lispro was injected at 0 min at doses that were adjusted appropriately for both the content of the standardized meal and the anticipated effects of pramlintide. Plasma glucose concentrations were measured before and during the 4-h postmeal period.
When injected at 0 min, pramlintide reduced the postprandial glucose excursion by 81% compared to insulin lispro + placebo (incremental AUC(0-4 h) (mean +/- SE) 2.0 +/- 1.5 vs. 10.4 +/- 2.2 mmol/h/L, P<0.05). When pramlintide was injected at -15, +15, and +30 min, the postprandial incremental glucose AUC(0-4 h) was also significantly reduced (P<0.05), but to a lesser extent (42 to 73%). Pramlintide treatment was well tolerated and no serious adverse events were reported.
Administration of pramlintide either at or just prior to a meal caused a greater reduction in postprandial glucose than either administration of placebo or postmeal pramlintide injections in subjects with type 2 diabetes treated with a rapid-acting insulin analog, insulin lispro.
评估人胰淀素类似物普兰林肽与赖脯胰岛素联合使用时对2型糖尿病患者的餐后降糖效果，重点关注相对于进餐的最佳给药剂量和时间。
在这项随机、单盲、安慰剂对照、五交叉试验中，19名使用赖脯胰岛素的2型糖尿病患者连续进行了五次混合餐试验。在过夜禁食后，受试者按照随机顺序在相对于标准化早餐前15分钟接受皮下注射安慰剂，或在相对于标准化早餐前15分钟、0分钟、15分钟或30分钟接受120微克普兰林肽注射。赖脯胰岛素在0分钟注射，剂量根据标准化餐食的含量和普兰林肽的预期效果进行适当调整。在餐后4小时内测量血浆葡萄糖浓度。
与赖脯胰岛素+安慰剂相比，在0分钟注射普兰林肽时，餐后血糖波动降低了81%（0至4小时的增量AUC（平均值±标准误）分别为2.0±1.5和10.4±2.2毫摩尔/小时/升，P<0.05）。当在-15分钟、15分钟和30分钟注射普兰林肽时，餐后增量葡萄糖AUC（0至4小时）也显著降低（P<0.05），但降低程度较小（42%至73%）。普兰林肽治疗耐受性良好，未报告严重不良事件。
在使用速效胰岛素类似物赖脯胰岛素治疗的2型糖尿病患者中，在进餐时或进餐前给予普兰林肽比给予安慰剂或餐后注射普兰林肽能更有效地降低餐后血糖。
