Edelman Steve, Garg Satish, Frias Juan, Maggs David, Wang Yan, Zhang Bei, Strobel Susan, Lutz Karen, Kolterman Orville
Division of Diabetes/Metabolism, San Diego VA Medical Center, San Diego, California, USA.
Diabetes Care. 2006 Oct;29(10):2189-95. doi: 10.2337/dc06-0042.
To assess safety, efficacy, and tolerability of pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes.
This 29-week, double-blind, placebo-controlled study randomized 296 patients to pramlintide or placebo as an adjunct to insulin. During initiation, pramlintide was escalated from 15 to 60 microg/meal (15-microg increments) with recommended reductions (30-50%) in mealtime insulin. Insulin was subsequently adjusted to optimize glycemic control. End points included safety and change in HbA1c (A1C), postprandial glucose, insulin, weight, and tolerability.
Baseline A1C was 8.1% for both groups and at week 29 had decreased comparably (pramlintide -0.5% [95% CI -0.61 to -0.33]; placebo -0.5% [-0.63 to -0.35]). Pramlintide treatment significantly reduced postprandial glucose excursions (incremental area under the curve AUC: pramlintide -175 +/- 40, placebo -64 +/- 38 mg x h(-1) x dl(-1); P < 0.0005) and weight (pramlintide -1.3 +/- 0.30, placebo +1.2 +/- 0.30 kg; P < 0.0001). At week 29, insulin dose decreased by 28 and 4% in pramlintide- and placebo-treated groups, respectively. Nausea, reported by 63 and 36% of patients in pramlintide and placebo groups (P < 0.01), respectively, was predominately mild to moderate in intensity. Severe hypoglycemia rates were low in both groups (pramlintide 0.57 +/- 0.09, placebo 0.30 +/- 0.06 event rate/patient-year; P < 0.05), with increased rates observed in patients remaining at 30 microg pramlintide.
Pramlintide dose escalation with reduced mealtime insulin was effective during therapy initiation in patients with type 1 diabetes. While both groups experienced equivalent A1C reductions relative to placebo, pramlintide-treated patients experienced reductions in postprandial glucose excursions and weight, not achievable with insulin therapy alone.
评估在1型糖尿病患者中，先减少餐时胰岛素剂量，随后优化胰岛素治疗的同时，逐步增加普兰林肽剂量的安全性、有效性和耐受性。
这项为期29周的双盲、安慰剂对照研究将296例患者随机分为普兰林肽组或安慰剂组，作为胰岛素治疗的辅助治疗。在起始阶段，普兰林肽剂量从每餐15微克逐步增加至60微克（每次增加15微克），同时按推荐减少餐时胰岛素剂量（减少30%-50%）。随后调整胰岛素剂量以优化血糖控制。终点指标包括安全性以及糖化血红蛋白（HbA1c，A1C）、餐后血糖、胰岛素、体重的变化和耐受性。
两组患者的基线A1C均为8.1%，在第29周时均有相似程度的下降（普兰林肽组下降0.5%[95%可信区间-0.61至-0.33]；安慰剂组下降0.5%[-0.63至-0.35]）。普兰林肽治疗显著降低了餐后血糖波动（曲线下增量面积AUC：普兰林肽组-175±40，安慰剂组-64±38毫克·小时⁻¹·分升⁻¹；P<0.0005）和体重（普兰林肽组-1.3±0.30，安慰剂组+1.2±0.30千克；P<0.0001）。在第29周时，普兰林肽治疗组和安慰剂治疗组的胰岛素剂量分别下降了28%和4%。普兰林肽组和安慰剂组分别有63%和36%的患者报告有恶心症状（P<0.01），恶心程度多为轻至中度。两组严重低血糖发生率均较低（普兰林肽组为0.57±0.09，安慰剂组为0.30±0.06事件发生率/患者年；P<0.05），普兰林肽剂量维持在30微克的患者中严重低血糖发生率有所增加。
在1型糖尿病患者治疗起始阶段，减少餐时胰岛素剂量并增加普兰林肽剂量是有效的。虽然两组相对于安慰剂而言，A1C降低程度相当，但接受普兰林肽治疗的患者餐后血糖波动和体重有所下降，这是单纯胰岛素治疗无法实现的。
