吸入式干粉胰岛素用于治疗糖尿病。

Setter Stephen M, Levien Terri L, Iltz Jason L, Odegard Peggy Soule, Neumiller Joshua J, Baker Danial E, Campbell R Keith

Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, Washington, USA; Elder Services, Spokane, Washington, USA.

Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, Washington, USA; Drug Information Center, Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, Washington, USA.

Clin Ther. 2007 May;29(5):795-813. doi: 10.1016/j.clinthera.2007.05.015.

BACKGROUND

Inhaled dry powder insulin (IDPI) is the first inhaled insulin approved for the treatment of type 1 and type 2 diabetes mellitus (DM).

OBJECTIVE

This article reviews available information on IDPI, focusing on its clinical pharmacokinetics, comparative efficacy, tolerability, adverse events, dosage and administration, and cost.

METHODS

MEDLINE (1966-July 2006) and Web of Science (1995-July 2006) were searched for original research and review articles published in English. The search terms used were inhaled insulin, inhaled human insulin, rDNA origin inhalation powder, inbaled dry powder insulin, and IDPI. All published comparative efficacy studies were included in the review, as well as selected information from the package insert for IDPI.

RESULTS

IDPI is an inhaled dry powder form of regular human insulin (RHI) that is used as a premeal insulin to improve glycemic control by reducing postprandial glucose excursions. The literature search identified 5 efficacy trials comparing reductions in glycosylated hemoglobin (HbA(1c)) in a total of 582 patients with type 1 DM who received either premeal IDPI plus neutral protamine Hagedorn (NPH) or Ultralente insulin or injectable RHI plus NPH or Ultralente insulin. The search identified 5 comparative efficacy studies of IDPI monotherapy or the addition of IDPI to the current regimen in a total of 1413 patients with type 2 DM that was uncontrolled with diet and exercise, metformin, a sulfonylurea, metformin and a sulfonylurea, or a secretagogue plus an insulin sensitizer. The use of IDPI as a mealtime insulin in these studies was associated with absolute changes in HbA(1c) ranging from -0.6% to +0.1% in patients with type 1 DM and from -1.4% to -2.9% in patients with type 2 DM. HbA(1c) values <7% were achieved in 16.9% to 28.2% of patients with type 1 DM and 16.7% to 44.0% of patients with type 2 DM. The most common nonrespiratory adverse event noted during clinical trials of IDPI was hypoglycemia (type 1 DM: 8.6-9.3 episodes/subject-month; type 2 DM: 0.3-1.4 episodes/subject-month), and the most common adverse event involving the pulmonary system was cough (21.9%-29.5%).

CONCLUSIONS

IDPI is the first available inhaled insulin. It provides an additional option for the achievement of HbA(1c) goals with a premeal insulin.

背景

吸入式干粉胰岛素（IDPI）是首个被批准用于治疗1型和2型糖尿病（DM）的吸入式胰岛素。

目的

本文回顾了关于IDPI的现有信息，重点关注其临床药代动力学、比较疗效、耐受性、不良事件、剂量与给药方法以及成本。

方法

检索MEDLINE（1966年 - 2006年7月）和科学引文索引（1995年 - 2006年7月），查找以英文发表的原创研究和综述文章。使用的检索词为吸入式胰岛素、吸入式人胰岛素、重组DNA来源吸入粉、吸入式干粉胰岛素和IDPI。所有已发表的比较疗效研究均纳入本综述，以及从IDPI药品说明书中选取的信息。

结果

IDPI是常规人胰岛素（RHI）的吸入式干粉剂型，用作餐时胰岛素，通过减少餐后血糖波动来改善血糖控制。文献检索确定了5项疗效试验，比较了总共582例1型糖尿病患者糖化血红蛋白（HbA1c）的降低情况，这些患者接受餐时IDPI加中性鱼精蛋白锌胰岛素（NPH）或长效胰岛素，或注射用RHI加NPH或长效胰岛素。检索确定了5项IDPI单药治疗或在当前治疗方案中加用IDPI的比较疗效研究，涉及总共1413例2型糖尿病患者，这些患者经饮食和运动、二甲双胍、磺脲类药物、二甲双胍和磺脲类药物，或促分泌剂加胰岛素增敏剂治疗未得到控制。在这些研究中，将IDPI用作餐时胰岛素，1型糖尿病患者的HbA1c绝对变化范围为 - 0.6%至 + 0.1%，2型糖尿病患者为 - 1.4%至 - 2.9%。1型糖尿病患者中16.9%至28.2%、2型糖尿病患者中16.7%至44.0%的患者HbA1c值<7%。在IDPI临床试验期间最常见的非呼吸道不良事件是低血糖（1型糖尿病：8.6 - 9.3次/受试者 - 月；2型糖尿病：0.3 - 1.4次/受试者 - 月），涉及肺部系统最常见的不良事件是咳嗽（21.9% - 29.5%）。