Amylin Pharmaceuticals, LLC, San Diego, CA 92121, USA.
Postgrad Med. 2013 May;125(3):136-44. doi: 10.3810/pgm.2013.05.2635.
To assess the safety and efficacy of the addition of pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM).
We conducted a post hoc analysis of 2 studies: a 29-week, multicenter, randomized, double-blind, placebo-controlled trial (referred to as RCT) (pramlintide, n = 82; placebo, n = 73) and an open-ended, multicenter, open-label, single-arm, observational study (referred to as clinical practice trial) (n = 150), which assessed the addition of pramlintide to CSII therapy in patients with T1DM. Pramlintide was initiated at 15 μg and titrated to 30 or 60 μg with major meals. The mealtime insulin dose was reduced by 30% to 50% at initiation, and then adjusted to optimize glycemic control. Endpoints at 29 weeks (RCT) and 6 months (clinical practice trial) included change in glycated hemoglobin (HbA1c) level, insulin dose, body weight, pre- and postprandial blood glucose level, and tolerability and safety.
In both studies, mean baseline age was approximately 42 years, duration of diabetes was 20 to 24 years, and HbA1c level was approximately 8%. Pramlintide reduced blood glucose excursions and improved the percentage of recorded postprandial blood glucose levels < 180 mg/dL. Mean (± standard deviation) reduction in HbA1c level in the clinical practice trial was -0.3% ± 0.1% (P < 0.0001), and in the RCT was similar between pramlintide- and placebo-treated patients (-0.4% ± 0.1% and -0.3% ± 0.1%, respectively). Glycemic improvements were accomplished, with reductions in mealtime insulin doses (RCT: pramlintide, -23.8% ± 5.2%; placebo, -3.2% ± 4.1%; P < 0.0005; clinical practice trial: -27.5% ± 2.9%; P < 0.0001) and body weight (RCT: pramlintide, -2.2 kg ± 0.5 kg; placebo, +1.4 kg ± 0.3 kg; P < 0.0001; clinical practice trial: -3.2 kg ± 0.4 kg; P < 0.0001). Short-lived nausea, primarily mild to moderate in intensity, was the most common adverse event associated with pramlintide therapy. Severe hypoglycemic events occurred at a rate of 0.56 and 0.34 events per patient-year in pramlintide- and placebo-treated patients, respectively, in the RCT, and at a rate of 0.12 events per patient-year in the clinical practice trial.
Addition of pramlintide to CSII therapy was safe and effective in patients with T1DM. Pramlintide should be considered for patients who are not able to optimize glycemic control with CSII therapy alone, particularly those with difficulty controlling postprandial blood glucose levels and/or body weight.
www.ClinicalTrials.gov identifiers: NCT00042458, NCT00108004.
评估普兰林肽联合持续皮下胰岛素输注（CSII）治疗 1 型糖尿病（T1DM）患者的安全性和有效性。
我们对两项研究进行了事后分析：一项 29 周、多中心、随机、双盲、安慰剂对照试验（称为 RCT）（普兰林肽组，n = 82；安慰剂组，n = 73）和一项开放、多中心、开放标签、单臂、观察性研究（称为临床实践试验）（n = 150），评估了普兰林肽联合 CSII 治疗 T1DM 患者的情况。普兰林肽起始剂量为 15 μg，并随餐滴定至 30 或 60 μg。起始时将餐时胰岛素剂量减少 30%至 50%，然后调整剂量以优化血糖控制。29 周（RCT）和 6 个月（临床实践试验）的终点包括糖化血红蛋白（HbA1c）水平、胰岛素剂量、体重、餐前和餐后血糖水平以及耐受性和安全性的变化。
在两项研究中，患者的平均基线年龄约为 42 岁，糖尿病病程约为 20 至 24 年，HbA1c 水平约为 8%。普兰林肽降低了血糖波动，并改善了餐后血糖水平 < 180 mg/dL 的记录百分比。临床实践试验中 HbA1c 水平的平均（±标准差）降低为-0.3% ± 0.1%（P < 0.0001），而在 RCT 中，普兰林肽和安慰剂治疗患者的 HbA1c 水平降低相似（-0.4% ± 0.1%和-0.3% ± 0.1%）。通过减少餐时胰岛素剂量（RCT：普兰林肽组，-23.8% ± 5.2%；安慰剂组，-3.2% ± 4.1%；P < 0.0005；临床实践试验：-27.5% ± 2.9%；P < 0.0001）和体重（RCT：普兰林肽组，-2.2 kg ± 0.5 kg；安慰剂组，+1.4 kg ± 0.3 kg；P < 0.0001；临床实践试验：-3.2 kg ± 0.4 kg；P < 0.0001），实现了血糖改善。与普兰林肽治疗相关的最常见不良事件是短暂性恶心，主要为轻至中度强度。在 RCT 中，普兰林肽和安慰剂治疗患者的严重低血糖事件发生率分别为 0.56 和 0.34 例/患者年，而在临床实践试验中为 0.12 例/患者年。
普兰林肽联合 CSII 治疗 T1DM 患者是安全有效的。对于不能单独通过 CSII 治疗优化血糖控制的患者，特别是那些难以控制餐后血糖水平和/或体重的患者，应考虑使用普兰林肽。
www.ClinicalTrials.gov 标识符：NCT00042458，NCT00108004。
