INHALED HUMAN INSULIN VERSUS USUAL SUBCUTANEOUS INSULIN

目的：本研究的目的是确定在1型糖尿病患者中，餐前吸入胰岛素加一次睡前注射Ultraalente的胰岛素方案是否能至少与传统的皮下注射胰岛素方案(每天2-3次注射)一样有效地实现血糖控制；以及吸入性胰岛素疗法的耐受性和安全性及其对肺功能指标的影响(如果有的话)(S)。方法：这是一项开放标签、为期3个月、平行的多中心研究。在这项研究中，共有60名1型糖尿病患者(所有地点的总数)将接受评估。成功完成为期3个月的对比试验的受试者将有资格接受开放标签方案的胰岛素吸入，该方案已连续延长两年。在对照试验中，对照条件是胰岛素注射治疗，根据受试者通常的(研究前)给药方案，给予BID或TID。研究条件是AC剂量吸入的人胰岛素加上一次睡前注射Ulalente。对于随机分为两组的受试者，胰岛素剂量将根据血糖监测结果进行调整以优化控制。在扩展研究中，患者可以选择返回皮下胰岛素，或者继续或开始吸入胰岛素。在为期3个月的试验中，胰岛素调整将基于血糖监测结果。安全参数包括每三个月进行一次肺功能测试，以及每年的EKG和胸部X光检查。将每4周进行一次临床检查，以便对试验的安全性和有效性进行监测。结果和结论：最初3个月的研究结果表明，吸入胰岛素耐受性良好，血糖控制与皮下注射胰岛素相当。这项为期3个月的研究结果以抽象的形式在6月举行的第58届美国糖尿病协会科学会议上公布。目前，受试者在第二次延长一年的研究中继续接受跟踪，研究赞助商计划继续延长研究，直到获得FDA的批准。意义：最近，糖尿病控制和并发症试验(DCCT)证明了严格控制血糖和积极的胰岛素治疗对糖尿病患者的长期益处。DCCT的结果显示，使用强化胰岛素疗法的胰岛素依赖者的糖尿病并发症显著减少。然而，尽管研究表明这种类型的治疗有好处，但积极的胰岛素治疗在临床实践中获得接受的速度很慢。患者接受性差是由于治疗的不便以及餐后胰岛素作用的不可预测性。因此，一种易于管理并提供可预测的胰岛素作用模式的吸入型胰岛素可能更容易被需要胰岛素治疗的患者接受，并可能提供更好的总体血糖控制。未来计划：研究赞助商辉瑞公司正在制定第三阶段研究计划。

PURPOSE: The purpose of this study is to determine in subjects with type 1 diabetes mellitus: whether glycemic control can be achieved at least as effectively with an insulin regimen involving pre-meal inhaled insulin plus a single bedtime Ultralente injection as with a conventional subcutaneous insulin regimen involving 2-3 injections per day; and the toleration and safety of inhaled insulin therapy and its effect(s), if any, on measures of pulmonary function. METHODS: This is an open-label, 3-month, parallel, multicenter study. A total of 60 subjects ( a total for all sites) with type 1 diabetes will be evaluated in this study. Subjects who successfully complete the 3-month comparative trial will be eligible to receive inhaled insulin in an open-label protocol which has been extended for two consecutive years. In the comparative trial the control condition is insulin injection therapy, given either BID or TID, depending upon the subject's usual (prestudy) administration regimen. The study condition is tid AC dosing of inhaled human insulin plus a single bedtime Ultralente injection. For subjects randomized to both groups, insulin doses will be adjusted to optimize control based on glucose monitoring results. In the extension study, patients may elect to return to subcutaneous insulin or to continue or start inhaled insulin. As in the 3-month trial, insulin adjustments will be based on glucose monitoring results. Safety parameters include pulmonary function testing performed every three months, as well as yearly EKG and chest X-ray. Clinic visits will occur every 4 weeks so that both the safety and efficacy of trial may be monitored. RESULTS AND CONCLUSIONS: Results from the initial 3-month study indicate that inhaled insulin is well- tolerated and glycemic control is comparable to insulin administered subcutaneously. The results of the 3-month study were presented in abstract form at the 58th Scientific Sessions of the American Diabetes Association, June. At the present time, subjects are continuing to be followed in the 2nd one-year extension of the study, and the study sponsor plans to continue extending the study until the FDA approval is obtained. SIGNIFICANCE: Recently, the long-term benefit of tight glycemic control with aggressive insulin therapy has been demonstrated in patients with diabetes in the Diabetes Control and Complications Trial (DCCT). Results from the DCCT showed a significant reduction in diabetic complications in insulin-dependent subjects using an intensified insulin regimen. However, despite studies showing the benefit of this type of therapy, aggressive insulin therapy has been slow to gain acceptance in clinical practice settings. The poor patient acceptance is due to inconvenience of the therapy as well as the unpredictability of insulin action post-prandially. Therefore, an inhaled insulin which is easy to administer and provides a predictable pattern of insulin action may be more acceptable to patients requiring insulin therapy and may provide better overall glycemic control. FUTURE PLANS: Plans for phase III studies are underway by the study sponsor, Pfizer, Inc.