Understanding inhaled Technosphere Insulin: Results of an early randomized trial in type 1 diabetes mellitus

Technosphere Insulin (TI) is an inhaled insulin. Studies comparing TI with short-acting insulin analogues provide important insights on efficacy, dosing, and time course of action.Planned enrollment of 230 subjects was limited to 138 due to premature study discontinuation. The primary efficacy endpoint was a noninferiority of glycosylated hemoglobin (HbA1c) of 0.4% for TI compared with insulin lispro (LIS) in a 16-week phase 3 randomized clinical trial in type 1 diabetes mellitus.HbA1c values were similar in the TI and LIS groups at the beginning of the trial (7.8% and 7.6%, respectively) and at trial endpoint (7.7% and 7.6%, respectively). Least squares mean changes from baseline were similar between study groups. Glucose values after a standard meal were significantly lower with TI in the first 90 minutes post meal compared with LIS. Mild or moderate hypoglycemia event rates were also significantly lower with TI compared with LIS (5.97 vs 8.01, respectively; P = .0269). Cough was the most commonly reported adverse event with TI. Pulmonary function as measured by forced expiratory volume in 1 second was not different between groups at baseline, 16 weeks, or 4 weeks off study drug.HbA1c was unchanged and overall glucose control was comparable between groups. Treatment with TI resulted in improved post-meal glucose and a lower risk of hypoglycemia compared with LIS.背景: Technosphere胰岛素(TI)是一种吸入型胰岛素。该研究将TI与短效胰岛素类似物进行比较，并对有关疗效、剂量和作用时间的关系进行分析。 方法: 由于研究提前终止，计划招募的230名受试者最后限于138名。在1型糖尿病患者为期16周的3期随机临床试验中，主要研究终点是TI的糖化血红蛋白(HbA1c)与赖脯胰岛素(LIS)相比的非劣效性为0.4%。 结果: TI和LIS组的HbA1c值在试验开始和终点时相似，在试验开始时分别为7.8%和7.6%，试验终点时分别为7.7%和7.6%。研究组之间最小二乘均值相对于基线的变化相似。与LIS相比，TI在标准餐后前90分钟内的血糖显著降低。与LIS相比，TI的轻度或中度低血糖事件发生率也显著降低(分别为5.97和8.01； P = 0.0269)。咳嗽是最常见的TI不良反应。用1秒用力呼气量测量的肺功能在基线、停药16周或停药4周组之间没有差异。 结论: 各组间的HbA1c没有变化，总体血糖控制水平相当。与LIS相比，TI治疗可改善餐后血糖，降低低血糖风险。.