INHALED HUMAN INSULIN IN TYPE 2 DM ON SULFONYLUREA AND/OR METFORMIN

目的：这项研究的目的是确定目前正在接受磺脲类药物和/或二甲双胍治疗的2型糖尿病患者(1)是否可以通过增加一种餐前吸入胰岛素方案来改善血糖控制(通过糖化血红蛋白降低至少1%来衡量)和(2)胰岛素吸入疗法的耐受性和安全性及其3个月后对肺功能指标的影响(如果有的话)。方法：总共有60名受试者将参与这项试验，其中约6名受试者将在该地点接受评估。在这项为期三个月的对比试验中，一半受试者将随机接受胰岛素吸入方案加研究前口服药物，而另一半受试者将继续接受研究前口服药物。成功完成这项为期三个月的试验的患者将有资格获得一年的开放标签协议延期。在进入研究之前，受试者要接受筛查，包括病史和体检、EKG、CXR和实验室检查，以验证患者是否有资格参加研究。这之后是4周的基线引导期，在此期间患者继续服用研究前的口服制剂。在此期间，受试者接受肺功能测试(PFT)、饮食指导和家庭血糖监测指导。所有患者都配备了血糖仪和血糖仪，并被要求每天进行4次血糖检查，记录剂量和血糖仪读数，并记录发生的任何低血糖或不良事件。在基准期结束时，受试者入院接受为期2天的住院治疗，在此期间，他们被指导如何使用该设备和吸入胰岛素剂量。在入院结束时，受试者被随机分成两组(餐前吸入胰岛素+口服降糖剂与餐前吸入安慰剂+口服药物)。随机分组是双盲的，并根据HbA1c进行分层。在治疗期间，每隔一周对患者进行随访。在治疗的前4周，患者必须每周返回诊所进行评估。在那之后，患者可能每隔一周回来一次。膳食挑战研究将在第0、4、8和12周进行，在此期间，患者将被要求摄入16盎司Susta饮料，并将收集测量血糖和游离胰岛素水平的定时血样。同样在诊所就诊时，将采集血样以评估HbA1c、空腹血糖、果糖胺和血脂。第6周将进行肺活量测定，第12周将重复一次完整的PFT电池。在可选的一年延期中，患者需要每月返回诊所就诊。PFT将每3个月进行一次。结果和结论：这项研究正在进行中，到目前为止还没有结果。意义：糖尿病控制和并发症试验(DCCT)证明了严格控制血糖的长期益处。然而，现有的SC给药方法的缺点限制了积极胰岛素治疗益处的临床实现。特别是，多次注射疗法的患者接受度很低。这项研究旨在确定餐前吸入胰岛素方案是否可以改善口服药物控制不良的患者的血糖控制。该系统的设计允许安全、非侵入性地在每次剂量中吸入1-2次快速作用的胰岛素。如果证明是安全和有效的，吸入型胰岛素，它易于管理并提供可预测的胰岛素作用模式，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，从而可能减少糖尿病并发症的发生率。研究赞助商辉瑞公司目前正在进行吸入型胰岛素的第三阶段研究计划。

PURPOSE: The purpose of this study is to determine, in subjects with type 2 diabetes mellitus currently receiving a sulfonylurea and /or metformin as therapy (1) whether glycemic control can be improved, as measured by a decrease of at least 1% in the glycosylated hemoglobin, by the addition of a regimen of pre-meal inhaled insulin and (2) the toleration and safety of inhaled insulin therapy and its effects after 3 months, if any, on measures of pulmonary function. METHODS: In total, 60 subjects will participate in this trial, with approximately 6 being evaluated at this site. During this three-month comparative trial, half of the subjects will be randomized to receive an inhaled insulin regimen plus pre-study oral agent while the other half will continue pre-study oral agent. Patients who successfully complete this three-month trial will be eligible for a one-year, open-label protocol extension. Prior to study entry, subjects undergo a screening session, including a history and physical exam, EKG, CXR, and lab studies to verify that the patient is eligible for participation. This is followed by a 4 week baseline lead-in period, during which patients continue their pre-study oral agent. Subjects undergo pulmonary function tests (PFTs), dietary instruction, and home blood glucose monitoring instruction during this time. All patients are provided with a glucose meter and supplies and are required to perform blood glucose checks 4 times/day, to record doses and meter readings, and to document any hypoglycemic or adverse events which occur. At the end of the baseline period, subjects are admitted for a 2 day inpatient session, during which they are instructed in the use of the device and dosing with inhaled insulin. At the end of the admission, subjects are randomized to one of two treatment groups (premeal inhaled insulin plus oral hypoglycemic agent vs premeal inhaled placebo plus oral agent). Randomization is double-blinded and is stratified based on HbA1c. During the treatment period, patients are followed at weekly intervals. For the first 4 weeks of treatment, patients must return to the clinic for evaluation every week. After that, patients may return once every other week. Meal challenge studies will be performed at weeks 0,4,8, and 12, during which a patient will be asked to consume 16 oz of Sustacal beverage and timed blood draws measuring blood glucose and free insulin levels will be collected. Also at clinic visits, blood samples will be collected to evaluate HbA1c, fasting blood glucose, fructosamine, and lipids. Spirometry will be performed at week 6, and a full PFT battery will be repeated at week 12. In the optional one year extension, patients are required to return for monthly clinic visits. PFT's will be performed every 3 months. RESULTS AND CONCLUSIONS: The study is ongoing, and results are not available to date. SIGNIFICANCE: The Diabetes Control and Complications Trial (DCCT) demonstrated the long-term benefits of tight glycemic control. However, the clinical realization of the benefits of aggressive insulin therapy has been limited by the shortcomings of available SC delivery methods. In particular, multiple injection therapy has had poor patient acceptance. This study aims to determine whether the addition of a pre-meal inhaled insulin regimen can provide improved glycemic control to patients poorly controlled on oral agents. This system is designed to permit safe, non-invasive delivery of rapid-acting insulin in 1-2 inhalations per dose. If proven to be safe and effective, 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 thereby possibly reducing the incidence of diabetic complications. Plans for phase III studies of inhaled insulin are currently underway by the study sponsor, Pfizer, Inc.