Efficacy and Safety of Inhaled Insulin Compared With Subcutaneous Human Insulin Therapy in Adults With Type 1 Diabetes

Change from Baseline: mean of (value of Glycosylated Hemoglobin [HbA1c] at observation minus Baseline value).

A Hypoglycemic event was identified by characteristic symptoms of hypoglycemia with no blood glucose check with prompt resolution with food intake, subcutaneous glucagon, or intravenouus glucose; characteristic symptoms with blood glucose of 59 milligrams per deciliter (mg/dL) (3.2 mmol/L) or less with blood glucose check; or any glucose measurement of 49 mg/dL (2.7 mmol/L) or less, with or without symptoms. Subject months = elapsed number of months a subject was in the study in each time interval. Crude event rate = total events divided by subject month of treatment.

Severe hypoglycemic event = all 3 of the following criteria were met: subject unable to treat self, exhbited at least 1 neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, loss of consciousness); and blood glucose measurement was ≤49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, subcutaneous glucagon, or i.v. glucose. Subject months = elapsed number of months subject was in study in each time interval. Crude event rate = total events divided by subject months * 100.

Change from Baseline: mean of (value of fasting plasma glucose [milligrams per deciliter (mg/dL)] at observation minus Baseline value).

Body weight: mean Baseline and change from Baseline in kilograms (kg). Change from baseline = mean body weight in kilograms (kg) at observation minus mean baseline body weight.

Total Daily Long-Acting Insulin Dose Unadjusted for Body Weight; long-acting insulin included NPH Insulin, Ultralente, and Insulin Glargine for both groups.

Total daily dose of long-acting insulin adjusted for body weight (units per kilogram [kg]). Long-acting insulin included NPH Insulin, Ultralente, and Insulin Glargine for both groups.

Total daily dose of short-acting insulin unadjusted for body weight. Short-acting insulin (mg) for the Inhaled Insulin group was Inhaled Insulin. Short-acting insulin (unit) for the Subcutaneous Insulin group included Insulin Lispro, Insulin Aspart, and Regular Insulin.

Total Daily Short-Acting Insulin Dose adjusted for body weight (milligrams [mg] or units divided by kilograms [kg]). Short-acting insulin (mg) for the Inhaled Insulin group was Inhaled Insulin. Short-acting insulin (unit) for the Subcutaneous Insulin group included Insulin Lispro, Insulin Aspart, and Regular Insulin.

Clinician administered instrument to measure the baseline severity of breathlessness (shortness of breath) in symptomatic patients with 3 domains: functional impairment, magnitude of task, and magnitude of effort. BDI score range 0 (very severe impairment) to 4 (no impairment) scaled to a BDI focal score (0-12). Lower score indicates greater impairment.

Clinician administered instrument to measure the baseline severity of breathlessness (shortness of breath) in symptomatic patients with 3 domains: functional impairment, magnitude of task, and magnitude of effort. TDI score range -3 (major deterioration) to +3 (major improvement); sum of all domains yields the TDI focal score (-9 to +9); lower score indicates greater deterioration. Compared to previous scoring to determine deterioration or improvement.

Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides measured as milligrams per deciliter (mg/dL).

Subject completed cough questionnaire with reference to the past 4 weeks. Six question instrument to measure cough frequency (night, day), severity, timing in relation to short-acting insulin dosing, severity related to insulin dosing (subcutaneous [SC] or inhaled), and productivity of cough; range 0 (no symptoms) to 4 (severe symptoms). Questionnaire was administered at Week 0 and then at subsequent visits only if cough was identified as an adverse event not explained by a concomitant condition, such as an upper respiratory tract infection.

Forced Vital Capacity (FVC) measured in liters (L).

Total Lung Capacity measured in liters (L).

Median insulin antibodies at each visit measured in micro units per milliliter (microU/mL).