A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics With Asthma

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00139659
• Collaborator: (none)
• Enrollment: 288
• Locations: 102
• Arms: 2
• Duration (Months): 69
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics with Asthma

Condition or Disease	Intervention/Treatment	Phase
Asthma; Diabetes Mellitus	Drug: Inhaled Insulin; Drug: Subcutaneous Insulin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 288 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Inhaled Human Insulin (Exubera) Compared With Subcutaneous Human Insulin in the Therapy of Adult Subjects With Type 1 or Type 2 Diabetes Mellitus and Chronic Asthma: A One-Year, Multicenter, Randomized, Outpatient, Open-Label, Parallel-Group Comparative Trial
• Study Start Date: Jan 1, 2003
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inhaled Insulin	Drug: Inhaled Insulin; Inhaled insulin with dose adjusted according to premeal blood glucose plus oral antidiabetic agent(s) and/or either once or twice daily doses of either Ultralente or NPH insulin, or a single bedtime dose of insulin glargine.
Active Comparator: Subcutaneous Insulin	Drug: Subcutaneous Insulin; Subcutaneous short-acting insulin with dose adjusted according to premeal blood glucose plus oral antidiabetic agent(s) and/or either once or twice daily doses of either Ultralente or neutral protamine hagedorn (NPH) insulin, or a single bedtime dose of insulin glargine.

Outcome Measures

Primary Outcome Measures

1. Annualized Rate of Change for Forced Expiratory Volume in 1 Second (FEV1) [Weeks -3, -2, -1, 1, 2, 3, 4, 6, 12, 18, 26, 39, and 52]

   Annualized rates of change (slope throughout time from baseline to end of study[visit]) for forced expiratory volume in 1 second (FEV1) (liters per year [L/yr]) measured 30 minutes following the administration of albuterol.

2. Annualized Rate of Change for Hemoglobin-adjusted Carbon Monoxide Diffusion Capacity (DLco) [Weeks -3, -2, -1, 1, 2, 3, 4, 6, 12, 18, 26, 39, and 52]

   Annualized rates of change (slope throughout time from baseline to end of study[visit]) for hemoglobin-adjusted carbon monoxide diffusion capacity (DLco)in milliliters per minute/millimeters of mercury/year (ml/min/mmHg/yr) measured 30 minutes following the administration of albuterol.

3. Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1) [Baseline through Week 52 Last Observation Carried Forward (LOCF)]

   Change from Baseline at each visit in post-bronchodilator forced expiratory volume in one second (FEV1). FEV1 was measured in liters (L) 30 minutes following the administration of albuterol. Change from baseline: mean FEV1 (L) at observation minus baseline value.

4. Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) [Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)]

   Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg) 30 minutes following the administration of albuterol. Change from Baseline: mean DLco (mL/min/mmHg) at observation minus baseline value.

Secondary Outcome Measures

1. Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) [Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)]

   Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) at each visit. FEV1 was measured in liters (L) before the administration of albuterol. Change from baseline: mean FEV1 (L) at observation minus mean baseline value.

2. Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) [Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation carried Forward (LOCF)]

   Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg): change = DLco at observation minus DLco at Baseline.

3. Change From Baseline in Pre-Insulin Forced Expiratory Volume in One Second (FEV1) [Baseline, Week 9, Week 51, Week 51 Last Observation Carried Forward]

   Change from Baseline in Pre-Insulin Forced Expiratory Volume in one second (FEV1) measured in liters (L): change = FEV1 at observation minus FEV1 at Baseline.

4. Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco) [Baseline, Week 9, Week 51, Week 51 Last Observation Carried Forward (LOCF)]

   Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg): change = DLco at observation minus DLco at Baseline.

5. Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) [Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)]

   Change from baseline in Post-bronchodilator Forced Vital Capacity (FVC) measured in liters (L) 30 minutes following the administration of albuterol: change = FVC at observation minus FVC at Baseline.

6. Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol [Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52]

   Responsiveness was the percent change from the forced expiratory volume in 1 second (FEV1) value before bronchodilator use to the FEV1 value 30 minutes after bronchodilator use, operationally defined as [(post-bronchodilator FEV1 minus pre-bronchodilator FEV1 divided by pre-bronchodilator FEV1] multiplied by 100.

7. Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1) [Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)]

   Percent predicted change from Baseline in post-bronchodilator forced expiratory volume in one second (FEV1) measured in liters (L): National Health and Nutrition Examination Survey (NHANES III) reference standard. Percent change from Baseline in post-bronchdilator FEV1 measured in liters (L): (observed value minus Baseline value) divided by Baseline value *100%.

8. Change From Baseline in Insulin Dose Responsiveness for Forced Expiratory Volume in One Second (FEV1) Measured 10 and 60 Minutes After the First Daily Dose of Insulin [Baseline, Week 9, Week 51]

   Change from Baseline in Insulin Dose Responsiveness for Forced Expiratory Volume in one second (FEV1) measured 10 and 60 minutes after the first daily dose of insulin. Insulin dose responsiveness = the difference between FEV1 value following a dose of insulin and FEV1 value before a dose of insulin, operationally defined as the post dose FEV1 value minus predose FEV1 value.

9. Percent Predicted and Percent Change From Baseline in 10 Minute and 60 Minute Post-Insulin Forced Expiratory Volume in One Second (FEV1) [Baseline, Week 9, Week 51, Week 51 Last Observation Carried Forward (LOCF)]

   Percent predicted change from Baseline in 10 Minute and 60 Minute post-insulin forced expiratory volume in one second (FEV1) measured in liters (L): National Health and Nutrition Examination Survey (NHANES III) reference standard. Percent change from Baseline in FEV1 measured in liters (L) 10 and 60 Minutes post-insulin. Percent change = (value at observation minus Baseline value) divided by Baseline value *100%.

10. Change From Baseline in Insulin Dose Responsiveness for Carbon Monoxide Diffusing Capacity (DLco) Measured 10 and 60 Minutes After the First Daily Dose of Insulin [Baseline, Week 9, Week 51]

    Carbon Monoxide Diffusing Capacity (DLco) dose responsivness 10 and 60 minutes after insulin. DLco dose-responsiveness to insulin was defined as the difference between the DLco value following a dose of insulin and DLco value before a dose of insulin, operationally defined as the post-dose DLco value minus pre-dose DLco value.

11. Methacholine Challenge [1 to 2 days following Weeks -3 and -1 visits, and at Week 11, Week 50, and Week 52 (+5)]

    Methacholine Challange: performed on a subset of subjects using the 5-breath dosimeter method. Subjects were challenged with ascending doses of nebulized methacholine; dosing schedule: 0.03, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0 milligrams per milliliter (mg/ml) administered in 5-minute intervals. Forced expiratory volume in 1 second (FEV1) was measured 1-3 minutes after each inhalation of methacholine solution. Testing continued until highest FEV1 decreased by ≥20% from the challenge (post-diluent) reference, or until completion all doses.

12. Mean Weekly Morning and Evening Peak Expiratory Flow Rate (PEFR) and Forced Expiratory Volume in 1 Second (FEV1) [Week -3 through Week 52]

    Subjects measured peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1) twice daily and entered the results in an electronic diary. Daily data were used to calculate the mean PEFR and FEV1 for each week (observed weekly mean and change from baseline in weekly mean). For each subject, the mean weekly morning (and evening) PEFR and FEV1 was defined as the sum of the daily morning (and evening) PEFR (and FEV1) measurements during the week divided by the number of non-missing PEFR (and FEV1) measurements during the week.

13. Mean Weekly Number of Puffs of Albuterol Used (Rescue Medication) [Daily: Baseline to end of study]

    All subjects used an electronic symptom diary to record their daily use of short-acting bronchodilators. Subjects recorded the sum of their short-acting bronchodilator use (puffs of albuterol) daily, immediately upon arising, and again in the evening or before bed.

14. Number of Subjects With Step-up and Step-down Changes in Classification of Asthma Severity by Medication Usage [Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52, Week 54, Week 58]

    All asthma medication changes during the study were classified as step-up or step-down according to treatment guidelines. Step 1: Intermittant Asthma; Step 2: Mild Persistent Asthma; Step 3: Moderate Persistent Asthma; Step 4: Severe Persistent Asthma. The number of subjects in each step classification of asthma severity were provided at each assessment timepoint for each treatment group, with a shift table indicating the number of subjects moving from each step classification at each timepoint.

15. Step Classification of Asthma Severity by Medication Usage [Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52, Week 54, Week 58]

    Step classification of asthma severity by medication usage. Subjects were classified at each visit according to the medication used on the day of the particular time-point; Step 1: intermittent asthma, Step 2: mild persistent asthma, Step 3: moderate persistent asthma, Step 4: severe persistent asthma. The number (%) of subjects in each step classification were provided at each assessment timepoint with a shift table indicating the number (%) of subjects moving from each step classification at each time-point.

16. Mean Weekly Asthma Symptom Scores [Baseline through end of study]

    Mean weekly asthma symptom scores: subjects recorded their asthma symptom scores in an electronic symptom diary twice daily throughout the study, immediately upon awakening (5-10 AM) and in the evening or at bedtime (7-12 PM). Questions included extent of albuterol use, symptoms of wheezing, coughing, activity limitations and sleep; scale 0 (none/fine) to 3 (severe/ continuous/bad night).

17. Incidence of Non-severe Asthma Exacerbations [0 to 1 week to > 12 months]

    Non-severe asthma exacerbation = one of the following: any home monitored morning (4:45 am - 10:15 am) forced expiratory volume in 1 second (FEV1) <80% of the morning baseline for 2 or more consecutive days; or home monitored FEV1 <60% of Baseline at any time. Percent of Baseline = 100*(daily FEV1)/Baseline weekly FEV1. Subject-months=elapsed number of months a subject was in the study in each time interval. Crude event rate = total events divided by subject-months.

18. Incidence of Severe Asthma Exacerbations [0 to 1 Week to > 12 Months]

    Severe asthma exacerbation was defined as one of the following: subject received oral (systemic) corticosteriods for the treatment of asthma; or subject had an unscheduled visit to a physician, emergency room, or hospital for the treatment of asthma. Subject-months=elapsed number of months a subject was in the study in each time interval. Crude event rate = total events divided by subject-months * 100.

19. Number of Systemic Corticosteroid Rescues [Baseline through Week 52]

    Number of subjects who used a systemic corticosteroid at any time during the study, and the total number of systemic corticosteroid rescues. New rescue event = >=2 consecutive days between the end of one event and the start of another event.

20. Asthma Control as Measured by the Asthma Control Questionnaire© [Baseline, Weeks 4, 12, 26, 39, 52]

    Asthma Control Questionnaire©: 6 self-administered questions that assess asthma control over the past week covering nocturnal waking, morning symptoms, activity limitations, shortness of breath, wheezing, and short-acting bronchodilator use; 7-point ordinal rating scale from 0 (good control) to 6 (poor control). A seventh question was completed by a health professional on forced expiratory volume in 1 second (FEV1) % predicted using a one-week recall period; scale: 0 (>95% predicted) to 6 (<50% predicted). Overall score = mean of questions 1 - 7.

21. Baseline Dyspnea Index (BDI) [run-in period]

    Total score = the sum of the numeric grades from the three dyspnea index questions. Functional Impairment rating scale: Grade 4 (no impairment) to Grade 0 (very severe impairment); Magnitude of Task rating scale: Grade 4 (extraordinary) to Grade 0 (no task); and Magnitude of Effort rating scale: Grade 4 (extraordinary) to grade 0 (no effort).

22. Transition Dyspnea Index (TDI): Change in Total Score [Week 4, Week 12, Week 26, Week 39, Week 52]

    Transition Dyspnea Index total score = sum of the numeric grades from the three dyspnea index questions: Change in Functional Impairment, Change in Magnitude of Task, and Change in Magnitude of Effort. Rating scale: -3 (major deterioration), -2 (moderate deterioration), -1 (minor deterioration, 0 (no change), +1 (minor improvement), +2 (moderate improvement), +3 (major improvement).

23. Glycosylated Hemoglobin (HbA1c) [Baseline, Week 6, Week 12, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)]

    Glycosylated Hemoglobin (HbA1c): observed mean values at Baseline and each observation, and change from Baseline. Change from Baseline = mean HbA1c at observation minus mean HbA1c at Baseline.

24. Fasting Plasma Glucose [Baseline, Week 6, Week 12, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)]

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

25. Body Weight: Mean Baseline and Change From Baseline [Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 11, Week 12, Week 18, Wek 26, Week 39, Week 50, Week 51, Week 52, Week 52 Last Observation Carried Forward (LOCF)]

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

26. Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) [Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52]

    Total Daily Long-Acting Insulin Dose Unadjusted for Body Weight: long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. Inhaled Insulin reported in mg. Subcutaneous Insulin reported in units.

27. Total Daily Long-Acting Insulin Dose Adjusted for Body Weight [Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52]

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

28. Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) [Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52]

    Average Total Daily Insulin Dose: short-acting insulin (milligrams [mg]). 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.

29. Total Daily Short-Acting Insulin Dose Adjusted for Body Weight [Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52]

    Total Daily Short-Acting Insulin Dose adjusted for body weight (units divided by 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.

30. Lipids: Median Change From Baseline to Last Observation [Baseline to Last Observation]

    Lipids: median changes (milligrams per deciliter [mg/dL]) from Baseline median to last observation in cholesterol (random), triglycerides (random), high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol. Normalized data was used in the computations. Last observation = last observation while on study drug or during the lag. Measures of dispersion for median changes in lipids were not determined.

31. Hypoglycemic Event Rates [0 to 1 month to 11 to 12 months, and Overall]

    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. Crude event rate = total events divided by subject months. Subject months = elapsed number of months a subject was in the study in each time interval.

32. Severe Hypoglycemic Event Rates [0 to 1 month to 11 to 12 months, and Overall]

    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); blood glucose measurement was ≤ 49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, subcutaneous glucagon, or i.v. glucose. Crude event rate = number of events divided by 100 subject-months. Subject months = elapsed number of months subject was in study in each time interval.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 77 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diabetes Mellitus (Type 1 or Type 2) currently controlled with injected insulin

• Mild intermittent or mild to moderate persistent asthma

Exclusion Criteria:

• Poorly controlled, unstable or steroid-dependent asthma, insulin pump therapy, smoking

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Glendale	Arizona	United States	85306
2	Pfizer Investigational Site	Peoria	Arizona	United States	85381
3	Pfizer Investigational Site	Phoenix	Arizona	United States	85004
4	Pfizer Investigational Site	Phoenix	Arizona	United States	85006
5	Pfizer Investigational Site	Phoenix	Arizona	United States	85016
6	Pfizer Investigational Site	Tucson	Arizona	United States	85715
7	Pfizer Investigational Site	Jonesboro	Arkansas	United States	72401
8	Pfizer Investigational Site	Searcy	Arkansas	United States	72143
9	Pfizer Investigational Site	Berkeley	California	United States	94705
10	Pfizer Investigational Site	Beverly Hills	California	United States	90211
11	Pfizer Investigational Site	Fresno	California	United States	93720
12	Pfizer Investigational Site	Greenbrae	California	United States	94904
13	Pfizer Investigational Site	Huntington Beach	California	United States	92648
14	Pfizer Investigational Site	Los Angeles	California	United States	90073
15	Pfizer Investigational Site	Riverside	California	United States	92506
16	Pfizer Investigational Site	San Diego	California	United States	92114
17	Pfizer Investigational Site	San Diego	California	United States	92116
18	Pfizer Investigational Site	Tustin	California	United States	92780
19	Pfizer Investigational Site	Boulder	Colorado	United States	80304
20	Pfizer Investigational Site	Denver	Colorado	United States	80206
21	Pfizer Investigational Site	Denver	Colorado	United States	80209
22	Pfizer Investigational Site	Denver	Colorado	United States	80220
23	Pfizer Investigational Site	Waterbury	Connecticut	United States	06708
24	Pfizer Investigational Site	Newark	Delaware	United States	19713
25	Pfizer Investigational Site	Chiefland	Florida	United States	32626
26	Pfizer Investigational Site	Clearwater	Florida	United States	33756
27	Pfizer Investigational Site	Clearwater	Florida	United States	33765
28	Pfizer Investigational Site	Melbourne	Florida	United States	32901
29	Pfizer Investigational Site	Miami	Florida	United States	33144
30	Pfizer Investigational Site	West Palm Beach	Florida	United States	33401
31	Pfizer Investigational Site	West Palm Beach	Florida	United States	33404
32	Pfizer Investigational Site	Augusta	Georgia	United States	30909
33	Pfizer Investigational Site	Honolulu	Hawaii	United States	96813
34	Pfizer Investigational Site	Honululu	Hawaii	United States	96814
35	Pfizer Investigational Site	Chicago	Illinois	United States	60611
36	Pfizer Investigational Site	Normal	Illinois	United States	61761
37	Pfizer Investigational Site	Evansville	Indiana	United States	47713
38	Pfizer Investigational Site	Indianapolis	Indiana	United States	46250
39	Pfizer Investigational Site	Des Moines	Iowa	United States	50314
40	Pfizer Investigational Site	Dubuque	Iowa	United States	52001
41	Pfizer Investigational Site	Dubuque	Iowa	United States	52002
42	Pfizer Investigational Site	Wichita	Kansas	United States	67203
43	Pfizer Investigational Site	Bossier City	Louisiana	United States	71111
44	Pfizer Investigational Site	North Dartmouth	Massachusetts	United States	02747
45	Pfizer Investigational Site	Springfield	Massachusetts	United States	01103
46	Pfizer Investigational Site	Springfield	Massachusetts	United States	01107
47	Pfizer Investigational Site	Waltham	Massachusetts	United States	02453
48	Pfizer Investigational Site	Brooklyn Center	Minnesota	United States	55430
49	Pfizer Investigational Site	St. Louis	Missouri	United States	63141
50	Pfizer Investigational Site	Butte	Montana	United States	59701
51	Pfizer Investigational Site	Henderson	Nevada	United States	89015
52	Pfizer Investigational Site	Las Vegas	Nevada	United States	89103
53	Pfizer Investigational Site	Las Vegas	Nevada	United States	89128
54	Pfizer Investigational Site	North Las Vegas	Nevada	United States	89032
55	Pfizer Investigational Site	Albuquerque	New Mexico	United States	87131-5666
56	Pfizer Investigational Site	Buffalo	New York	United States	14209
57	Pfizer Investigational Site	New York	New York	United States	10029
58	Pfizer Investigational Site	Cincinnati	Ohio	United States	45219
59	Pfizer Investigational Site	Cincinnati	Ohio	United States	45231
60	Pfizer Investigational Site	Cincinnati	Ohio	United States	45242
61	Pfizer Investigational Site	Dayton	Ohio	United States	45402
62	Pfizer Investigational Site	Toledo	Ohio	United States	43606
63	Pfizer Investigational Site	Toledo	Ohio	United States	43608
64	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73103
65	Pfizer Investigational Site	Medford	Oregon	United States	97504
66	Pfizer Investigational Site	Portland	Oregon	United States	97210
67	Pfizer Investigational Site	Portland	Oregon	United States	97219
68	Pfizer Investigational Site	Lansdale	Pennsylvania	United States	19446
69	Pfizer Investigational Site	Pittsburgh	Pennsylvania	United States	15243
70	Pfizer Investigational Site	Spartanburg	South Carolina	United States	29303
71	Pfizer Investigational Site	Spartanburg	South Carolina	United States	29307
72	Pfizer Investigational Site	Bartlett	Tennessee	United States	38133
73	Pfizer Investigational Site	Memphis	Tennessee	United States	38119
74	Pfizer Investigational Site	Nashville	Tennessee	United States	37203
75	Pfizer Investigational Site	Beaumont	Texas	United States	77701
76	Pfizer Investigational Site	Dallas	Texas	United States	75231
77	Pfizer Investigational Site	Houstan	Texas	United States	77079
78	Pfizer Investigational Site	Houston	Texas	United States	77030
79	Pfizer Investigational Site	Houston	Texas	United States	77043
80	Pfizer Investigational Site	San Antonio	Texas	United States	78229
81	Pfizer Investigational Site	San Antonio	Texas	United States	78237
82	Pfizer Investigational Site	Norfolk	Virginia	United States	23502
83	Pfizer Investigational Site	Richmond	Virginia	United States	23229
84	Pfizer Investigational Site	Richmond	Virginia	United States	23235
85	Pfizer Investigational Site	Spokane	Washington	United States	99202
86	Pfizer Investigational Site	Spokane	Washington	United States	99204
87	Pfizer Investigational Site	Porto Alegre	RS	Brazil	90035-170
88	Pfizer Investigational Site	SP	Sao Paulo	Brazil	04231-030
89	Pfizer Investigational Site	Campinas	SP	Brazil	13083-900
90	Pfizer Investigational Site	Sao Paulo	SP	Brazil	01244-030
91	Pfizer Investigational Site	Edmonton	Alberta	Canada	T5J 3N4
92	Pfizer Investigational Site	Red Deer	Alberta	Canada	T4N 6V7
93	Pfizer Investigational Site	Victoria	British Columbia	Canada	V8R 1J8
94	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3A 1R9
95	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3E 3P4
96	Pfizer Investigational Site	Burlington	Ontario	Canada	L7M 4Y1
97	Pfizer Investigational Site	London	Ontario	Canada	N6A 4V2
98	Pfizer Investigational Site	Laval	Quebec	Canada	H7T 2P5
99	Pfizer Investigational Site	Montreal	Quebec	Canada	H1T 2M4
100	Pfizer Investigational Site	Sherbrooke	Quebec	Canada	J1H 5N4
101	Pfizer Investigational Site	San Jose		Costa Rica
102	Pfizer Investigational Site	Neuss		Germany	41460

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00139659
• Other Study ID Numbers: A2171028
• First Posted: Aug 31, 2005
• Last Update Posted: Jun 2, 2010
• Last Verified: Oct 1, 2009

• Additional relevant MeSH terms: Asthma; Diabetes Mellitus; Insulin; Insulin, Globin Zinc

Study Results

Participant Flow

Recruitment Details	Subjects were recruited at 63 centers and participated in the study between 10 January 2003 and 22 October 2008.
Pre-assignment Detail	544 subjects were screened for the study. Prior to randomization subjects completed a 3-week run-in period during which all subjects received subcutaneous insulin. Of 288 subjects randomized, only 286 received randomized treatment; one subject assigned to inhaled insulin received subcutaneous insulin, and 1 subject DC'd prior to treatment.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Period Title: Overall Study
STARTED	146	141
COMPLETED	106	123
NOT COMPLETED	40	18

Baseline Characteristics

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin	Total
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.	Total of all reporting groups
Overall Participants	146	141	287
Age, Customized (participants) [Number]
18-25 years	12 8.2%	8 5.7%	20 7%
26-35 years	18 12.3%	13 9.2%	31 10.8%
36-45 years	23 15.8%	25 17.7%	48 16.7%
46-55 years	33 22.6%	41 29.1%	74 25.8%
56-65 years	40 27.4%	37 26.2%	77 26.8%
66-75 years	20 13.7%	17 12.1%	37 12.9%
Sex: Female, Male (Count of Participants)
Female	97 66.4%	91 64.5%	188 65.5%
Male	49 33.6%	50 35.5%	99 34.5%

Outcome Measures

1. Primary Outcome

Title	Annualized Rate of Change for Forced Expiratory Volume in 1 Second (FEV1)
Description	Annualized rates of change (slope throughout time from baseline to end of study[visit]) for forced expiratory volume in 1 second (FEV1) (liters per year [L/yr]) measured 30 minutes following the administration of albuterol.
Time Frame	Weeks -3, -2, -1, 1, 2, 3, 4, 6, 12, 18, 26, 39, and 52

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS): all subjects who were randomized, had no significant protocol violations, had baseline (BL) post-albuterol pulmonary function test (PFT) measurement, had at least 2 post-BL, post-albuterol PFT measurements with 1 measurement at least 6 months post-BL, and received study drug for at least 50% (154 days) of study duration.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	117	127
Mean (Standard Error) [L/yr]	-0.070 (0.020)	-0.035 (0.019)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Treatment group difference (Exubera minus subcutaneous insulin): annualized rate of change over time. Longitudinal data analysis methods with random effects were used to model the pulmonary function test (PFT) measurements. Random effects included the intercept and slope with respect to time (visit); all remaining effects were fixed. The estimated rate of change over time for each treatment group was derived from this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.034
	Confidence Interval	() 90%; -0.080 to 0.011
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.028
	Estimation Comments	Primary analysis model includes terms of Treatment, Time, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on day of randomization.

2. Secondary Outcome

Title	Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1)
Description	Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) at each visit. FEV1 was measured in liters (L) before the administration of albuterol. Change from baseline: mean FEV1 (L) at observation minus mean baseline value.
Time Frame	Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
Baseline (141, 139)	2.435 (0.748)	2.412 (0.727)
Week 1 (123, 125)	-0.057 (0.142)	-0.035 (0.131)
Week 2 (n=127, 117)	-0.065 (0.159)	-0.034 (0.150)
Week 3 (n=130, 121)	-0.067 (0.185)	-0.044 (0.171)
Week 4 (n=123, 130)	-0.076 (0.185)	-0.037 (0.181)
Week 6 (n=130, 135)	-0.059 (0.211)	-0.034 (0.170)
Week 12 (n=125, 130)	-0.067 (0.237)	-0.032 (0.193)
Week 18 (n=125, 125)	-0.063 (0.218)	-0.042 (0.183)
Week 26 (n=120, 129)	-0.058 (0.190)	-0.043 (0.195)
Week 39 (n=108, 124)	-0.076 (0.195)	-0.044 (0.186)
Week 52 (n=106, 112)	-0.136 (0.259)	-0.056 (0.230)
Week 52 LOCF (n=141, 139)	-0.119 (0.259)	-0.058 (0.222)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 1; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.025
	Confidence Interval	() 90%; -0.065 to 0.015
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 2; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.034
	Confidence Interval	() 90%; -0.073 to 0.006
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 3; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.024
	Confidence Interval	() 90%; -0.063 to 0.016
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 4; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.035
	Confidence Interval	() 90%; -0.075 to 0.004
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.027
	Confidence Interval	() 90%; -0.067 to 0.012
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.033
	Confidence Interval	() 90%; -0.073 to 0.008
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.025
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 18; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.018
	Confidence Interval	() 90%; -0.059 to 0.023
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.025
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.010
	Confidence Interval	() 90%; -0.052 to 0.031
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.025
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.025
	Confidence Interval	() 90%; -0.068 to 0.017
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.026
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.073
	Confidence Interval	() 90%; -0.117 to -0.029
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.027
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52 (LOCF); Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.061
	Confidence Interval	() 90%; -0.108 to -0.015
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.028
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco)
Description	Change From Baseline in Pre-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg): change = DLco at observation minus DLco at Baseline.
Time Frame	Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
Baseline (n=141, 139)	23.034 (5.921)	22.911 (6.059)
Week 1 (n=123, 125)	-0.749 (1.467)	-0.452 (1.220)
Week 2 (n=126, 114)	-0.835 (1.353)	-0.456 (1.485)
Week 3 (n=128, 119)	-0.855 (1.407)	-0.556 (1.452)
Week 4 (n=122, 127)	-1.120 (1.609)	-0.648 (1.500)
Week 6 (n=129, 135)	-1.169 (1.583)	-0.669 (1.441)
Week 12 (n=124, 128)	-1.018 (1.842)	-0.725 (1.788)
Week 18 (n=123, 125)	-0.906 (1.756)	-0.646 (1.748)
Week 26 (n=117, 127)	-0.945 (1.683)	-0.561 (1.982)
Week 39 (n=106, 125)	-0.821 (1.742)	-0.550 (1.805)
Week 52 (n=105, 111)	-1.699 (2.157)	-0.911 (2.239)
Week 52 LOCF (n=141, 139)	-1.557 (2.109)	-0.785 (2.141)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 1; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.327
	Confidence Interval	() 90%; -0.679 to 0.026
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.214
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 2; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.378
	Confidence Interval	() 90%; -0.729 to -0.027
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.213
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 3; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.346
	Confidence Interval	() 90%; -0.696 to 0.004
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.213
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 4; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.496
	Confidence Interval	() 90%; -0.847 to -0.145
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.213
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.610
	Confidence Interval	() 90%; -0.960 to -0.260
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.213
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.360
	Confidence Interval	() 90%; -0.721 to 0.001
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.219
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 18; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.291
	Confidence Interval	() 90%; -0.655 to 0.073
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.221
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.420
	Confidence Interval	() 90%; -0.788 to -0.052
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.224
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.337
	Confidence Interval	() 90%; -0.717 to 0.042
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.231
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.789
	Confidence Interval	() 90%; -1.181 to -0.397
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.238
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52 (LOCF); Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.786
	Confidence Interval	() 90%; -1.178 to -0.393
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.238
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Pre-Insulin Forced Expiratory Volume in One Second (FEV1)
Description	Change from Baseline in Pre-Insulin Forced Expiratory Volume in one second (FEV1) measured in liters (L): change = FEV1 at observation minus FEV1 at Baseline.
Time Frame	Baseline, Week 9, Week 51, Week 51 Last Observation Carried Forward

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	130	133
Baseline (n=130, 133)	2.449 (0.775)	2.403 (0.727)
Week 9 (n=111, 108)	-0.038 (0.235)	-0.028 (0.163)
Week 51 (n=103, 119)	-0.078 (0.227)	-0.017 (0.245)
Week 51 LOCF (n=130, 133)	-0.068 (0.237)	-0.018 (0.237)

5. Secondary Outcome

Title	Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco)
Description	Change From Baseline in Pre-Insulin Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg): change = DLco at observation minus DLco at Baseline.
Time Frame	Baseline, Week 9, Week 51, Week 51 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	128	131
Baseline (n=128, 131)	22.836 (6.087)	22.718 (6.128)
Week 9 (n=109, 106)	-1.130 (1.663)	-0.663 (1.549)
Week 51 (n=102, 116)	-1.156 (1.825)	-0.630 (2.023)
Week 51 LOCF (n=128, 131)	-1.185 (1.804)	-0.533 (1.990)

6. Secondary Outcome

Title	Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)
Description	Change from baseline in Post-bronchodilator Forced Vital Capacity (FVC) measured in liters (L) 30 minutes following the administration of albuterol: change = FVC at observation minus FVC at Baseline.
Time Frame	Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
Baseline (n=141, 139)	3.355 (0.963)	3.341 (0.918)
Week 1 (n=123, 125)	-0.068 (0.181)	-0.046 (0.134)
Week 2 (n=126, 115)	-0.057 (0.190)	-0.053 (0.169)
Week 3 (n=131, 119)	-0.078 (0.205)	-0.068 (0.174)
Week 4 (n=121, 129)	-0.065 (0.193)	-0.051 (0.176)
Week 6 (n=130, 135)	-0.092 (0.287)	-0.043 (0.173)
Week 12 (n=125, 129)	-0.045 (0.222)	-0.056 (0.190)
Week 18 (n=124, 125)	-0.053 (0.225)	-0.069 (0.179)
Week 26 (n=120, 128)	-0.061 (0.215)	-0.052 (0.186)
Week 39 (n=107, 124)	-0.080 (0.209)	-0.057 (0.213)
Week 52 (n=106, 112)	-0.105 (0.288)	-0.088 (0.259)
Week 52 LOCF (n=141, 139)	-0.097 (0.278)	-0.083 (0.247)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 1; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.021
	Confidence Interval	() 90%; -0.066 to 0.023
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.027
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 2; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.000
	Confidence Interval	() 90%; -0.044 to 0.044
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.027
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 3; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.012
	Confidence Interval	() 90%; -0.056 to 0.032
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.027
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 4; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.004
	Confidence Interval	() 90%; -0.048 to 0.041
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.027
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.045
	Confidence Interval	() 90%; -0.089 to -0.001
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.027
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.010
	Confidence Interval	() 90%; -0.035 to 0.056
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.028
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 18; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.018
	Confidence Interval	() 90%; -0.028 to 0.064
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.028
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.005
	Confidence Interval	() 90%; -0.051 to 0.041
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.028
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.022
	Confidence Interval	() 90%; -0.070 to 0.026
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.029
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.015
	Confidence Interval	() 90%; -0.064 to 0.034
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.030
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52 (LOCF); Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.015
	Confidence Interval	() 90%; -0.067 to 0.037
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.031
	Estimation Comments

7. Secondary Outcome

Title	Bronchodilator Responsiveness as Determined by the Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-albuterol and 30 Minutes Post-albuterol
Description	Responsiveness was the percent change from the forced expiratory volume in 1 second (FEV1) value before bronchodilator use to the FEV1 value 30 minutes after bronchodilator use, operationally defined as [(post-bronchodilator FEV1 minus pre-bronchodilator FEV1 divided by pre-bronchodilator FEV1] multiplied by 100.
Time Frame	Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
Baseline (n=141, 139)	5.487 (5.163)	5.102 (6.416)
Week 1 (n=123, 125)	-0.015 (5.452)	0.347 (5.429)
Week 2 (n=126, 115)	0.683 (5.984)	0.347 (6.354)
Week 3 (n=130, 119)	-0.055 (6.082)	0.823 (5.449)
Week 4 (n=121, 129)	0.056 (6.361)	0.559 (5.733)
Week 6 (n=130, 135)	-0.460 (5.480)	0.504 (6.350)
Week 12 (n=124, 129)	0.721 (5.972)	-0.100 (6.783)
Week 18 (n=124, 125)	-0.095 (5.909)	0.154 (7.649)
Week 26 (n=120, 128)	-0.186 (5.624)	0.211 (5.080)
Week 39 (n=107, 124)	-0.283 (5.368)	0.133 (5.089)
Week 52 (n=106, 112)	0.640 (5.338)	-0.035 (6.156)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 1; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.632
	Confidence Interval	() 90%; -1.778 to 0.514
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.697
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 2; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.020
	Confidence Interval	() 90%; -1.079 to 1.120
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.668
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 3; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.582
	Confidence Interval	() 90%; -0.535 to 1.700
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.679
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 4; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.054
	Confidence Interval	() 90%; -1.184 to 1.077
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.687
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.535
	Confidence Interval	() 90%; -1.677 to 0.608
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.694
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.905
	Confidence Interval	() 90%; -2.014 to 0.203
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.674
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 18; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.212
	Confidence Interval	() 90%; -0.899 to 1.323
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.675
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.044
	Confidence Interval	() 90%; -1.080 to 1.169
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.683
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.240
	Confidence Interval	() 90%; -1.382 to 0.902
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.694
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.503
	Confidence Interval	() 90%; -1.673 to 0.668
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.711
	Estimation Comments

8. Secondary Outcome

Title	Percent Predicted and Percent Change From Baseline in Post-Bronchdilator Forced Expiratory Volume in One Second (FEV1)
Description	Percent predicted change from Baseline in post-bronchodilator forced expiratory volume in one second (FEV1) measured in liters (L): National Health and Nutrition Examination Survey (NHANES III) reference standard. Percent change from Baseline in post-bronchdilator FEV1 measured in liters (L): (observed value minus Baseline value) divided by Baseline value *100%.
Time Frame	Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
Baseline (n=141, 139)	83.698 (14.096)	82.833 (15.219)
Week 1: % of Predicted Value (n=123, 125)	81.987 (14.441)	82.878 (15.438)
Week 2: % of Predicted Value (n=126, 115)	81.655 (13.985)	81.881 (15.017)
Week 3: % of Predicted Value (n=131, 119)	80.711 (13.854)	82.036 (15.354)
Week 4: % of Predicted Value (n=121, 129)	81.093 (15.145)	82.029 (14.914)
Week 6: % of Predicted Value (n=130, 135)	81.611 (14.553)	82.016 (15.509)
Week 12: % of Predicted Value (n=125, 129)	82.145 (13.885)	81.640 (14.673)
Week 18: % of Predicted Value (n=124, 125)	82.187 (14.405)	81.723 (14.505)
Week 26: % of Predicted Value (n=120, 128)	82.941 (14.291)	82.227 (14.305)
Week 39: % of Predicted Value (n=107, 124)	82.851 (14.447)	81.847 (14.794)
Week 52: % of Predicted Value (n=106, 112)	80.869 (14.934)	81.138 (14.461)
Week 52 LOCF: % of Predicted Value (n=141, 139)	80.136 (14.528)	80.687 (14.671)
Week 1: % Change from Baseline (n=123, 125)	-2.682 (5.780)	-1.238 (5.307)
Week 2: % Change from Baseline (n=126, 115)	-2.355 (5.909)	-1.142 (5.273)
Week 3: % Change from Baseline (n=131, 119)	-2.943 (7.583)	-1.057 (5.292)
Week 4: % Change from Baseline (n=121, 129)	-3.063 (6.926)	-0.833 (6.172)
Week 6: % Change from Baseline (n=130, 135)	-2.559 (8.725)	-0.957 (6.180)
Week 12: % Change from Baseline (n=125, 129)	-1.975 (8.495)	-1.226 (7.603)
Week 18: % Change from Baseline (n=124, 125)	-2.437 (8.713)	-1.247 (6.688)
Week 26: % Change from Baseline (n=120, 128)	-2.006 (6.891)	-1.189 (8.013)
Week 39: % Change from Baseline (n=107, 124)	-3.144 (7.507)	-1.466 (8.332)
Week 52: % Change from Baseline (n=106, 112)	-4.777 (8.794)	-2.002 (10.040)
Week 52 LOCF: % Change from Baseline (n=141, 139)	-4.129 (9.673)	-2.108 (9.652)

9. Secondary Outcome

Title	Change From Baseline in Insulin Dose Responsiveness for Forced Expiratory Volume in One Second (FEV1) Measured 10 and 60 Minutes After the First Daily Dose of Insulin
Description	Change from Baseline in Insulin Dose Responsiveness for Forced Expiratory Volume in one second (FEV1) measured 10 and 60 minutes after the first daily dose of insulin. Insulin dose responsiveness = the difference between FEV1 value following a dose of insulin and FEV1 value before a dose of insulin, operationally defined as the post dose FEV1 value minus predose FEV1 value.
Time Frame	Baseline, Week 9, Week 51

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	124	131
Baseline: 10 minutes (n=124, 131)	-0.004 (0.085)	0.003 (0.086)
Week 9: 10 minutes (n=105, 106)	-0.008 (0.130)	0.005 (0.111)
Week 51: 10 minutes (n=96, 113)	0.000 (0.113)	0.013 (0.104)
Baseline: 60 minutes (n=125, 131)	-0.004 (0.120)	0.016 (0.130)
Week 9: 60 minutes (n=105, 105)	0.013 (0.113)	0.028 (0.137)
Week 51: 60 minutes (n=99, 112)	0.029 (0.139)	0.020 (0.123)

10. Secondary Outcome

Title	Percent Predicted and Percent Change From Baseline in 10 Minute and 60 Minute Post-Insulin Forced Expiratory Volume in One Second (FEV1)
Description	Percent predicted change from Baseline in 10 Minute and 60 Minute post-insulin forced expiratory volume in one second (FEV1) measured in liters (L): National Health and Nutrition Examination Survey (NHANES III) reference standard. Percent change from Baseline in FEV1 measured in liters (L) 10 and 60 Minutes post-insulin. Percent change = (value at observation minus Baseline value) divided by Baseline value *100%.
Time Frame	Baseline, Week 9, Week 51, Week 51 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	124	131
Baseline: 10 minutes (n=124, 131)	94.402 (6.532)	94.391 (6.168)
Week 9: 10 min.; % of Predicted Value (n=105, 106)	92.698 (9.187)	94.190 (7.190)
Week 9: 10 min;% Change from Baseline (n=105, 106)	-1.864 (9.684)	-0.456 (8.638)
Week 51: 10 min.;% of Predicted Value (n=96, 113)	91.668 (8.223)	93.717 (9.305)
Week 51:10 min;% Change from Baseline (n=96, 113)	-2.760 (8.789)	0.228 (13.653)
Week 51 LOCF:10 min;% Predicted Value (n=124, 131)	91.196 (8.366)	93.882 (9.013)
Week 51 LOCF:10 min;% Change from BL (n=124, 131)	-3.176 (8.825)	-0.029 (12.946)
Baseline: 60 minutes (n=125, 131)	94.284 (6.548)	94.688 (5.260)
Week 9: 60 min.; % of Predicted Value (n=105, 105)	93.586 (8.219)	94.950 (7.526)
Week 9: 60 min;% Change from Baseline (n=105, 105)	-0.450 (9.464)	-0.031 (7.497)
Week 51: 60 min.; % of Predicted Value (n=99, 112)	92.302 (7.949)	94.084 (9.069)
Week 51:60 min.;% Change from Baseline (n=99, 112)	-1.699 (9.015)	-0.247 (10.349)
Week 51 LOCF:60 min;% Predicted Value (n=125, 131)	92.418 (8.544)	94.300 (8.823)
Week 51 LOCF:60 min;% Change from BL (n=125, 131)	-1.714 (9.512)	-0.222 (9.816)

11. Secondary Outcome

Title	Change From Baseline in Insulin Dose Responsiveness for Carbon Monoxide Diffusing Capacity (DLco) Measured 10 and 60 Minutes After the First Daily Dose of Insulin
Description	Carbon Monoxide Diffusing Capacity (DLco) dose responsivness 10 and 60 minutes after insulin. DLco dose-responsiveness to insulin was defined as the difference between the DLco value following a dose of insulin and DLco value before a dose of insulin, operationally defined as the post-dose DLco value minus pre-dose DLco value.
Time Frame	Baseline, Week 9, Week 51

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	122	129
Baseline: 10 minutes (n=122, 129)	-0.163 (0.992)	-0.184 (0.985)
Week 9: 10 minutes (n=102, 104)	-0.241 (1.390)	-0.131 (1.006)
Week 51: 10 minutes (n=95, 109)	-0.139 (0.893)	-0.171 (0.820)
Baseline: 60 minutes (n=135, 133)	-0.446 (1.115)	-0.451 (1.258)
Week 9: 60 minutes (n=104, 108)	-0.338 (1.416)	-0.159 (1.126)
Week 51: 60 minutes (n=101, 110)	-0.216 (1.458)	-0.383 (1.030)

12. Secondary Outcome

Title	Methacholine Challenge
Description	Methacholine Challange: performed on a subset of subjects using the 5-breath dosimeter method. Subjects were challenged with ascending doses of nebulized methacholine; dosing schedule: 0.03, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0 milligrams per milliliter (mg/ml) administered in 5-minute intervals. Forced expiratory volume in 1 second (FEV1) was measured 1-3 minutes after each inhalation of methacholine solution. Testing continued until highest FEV1 decreased by ≥20% from the challenge (post-diluent) reference, or until completion all doses.
Time Frame	1 to 2 days following Weeks -3 and -1 visits, and at Week 11, Week 50, and Week 52 (+5)

Outcome Measure Data

Analysis Population Description

There were no methacholine challenges performed in subjects using inhaled insulin due to protocol-defined exclusion criteria for methacholine challenge testing, and methacholine provocative concentration [of methacholine] causing a 20% fall in FEV1 (PC20) data were not analyzed.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	0	0

13. Secondary Outcome

Title	Mean Weekly Morning and Evening Peak Expiratory Flow Rate (PEFR) and Forced Expiratory Volume in 1 Second (FEV1)
Description	Subjects measured peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1) twice daily and entered the results in an electronic diary. Daily data were used to calculate the mean PEFR and FEV1 for each week (observed weekly mean and change from baseline in weekly mean). For each subject, the mean weekly morning (and evening) PEFR and FEV1 was defined as the sum of the daily morning (and evening) PEFR (and FEV1) measurements during the week divided by the number of non-missing PEFR (and FEV1) measurements during the week.
Time Frame	Week -3 through Week 52

Outcome Measure Data

Analysis Population Description

Mean weekly morning and evening peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1) were not presented due to lack of resource resulting from scaling down of Exubera® (inhaled insulin) development.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	0	0

14. Secondary Outcome

Title	Mean Weekly Number of Puffs of Albuterol Used (Rescue Medication)
Description	All subjects used an electronic symptom diary to record their daily use of short-acting bronchodilators. Subjects recorded the sum of their short-acting bronchodilator use (puffs of albuterol) daily, immediately upon arising, and again in the evening or before bed.
Time Frame	Daily: Baseline to end of study

Outcome Measure Data

Analysis Population Description

Mean weekly number of puffs of albuterol was not presented due to lack of resource resulting from scaling down of Exubera® (inhaled insulin) development.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	0	0

15. Secondary Outcome

Title	Number of Subjects With Step-up and Step-down Changes in Classification of Asthma Severity by Medication Usage
Description	All asthma medication changes during the study were classified as step-up or step-down according to treatment guidelines. Step 1: Intermittant Asthma; Step 2: Mild Persistent Asthma; Step 3: Moderate Persistent Asthma; Step 4: Severe Persistent Asthma. The number of subjects in each step classification of asthma severity were provided at each assessment timepoint for each treatment group, with a shift table indicating the number of subjects moving from each step classification at each timepoint.
Time Frame	Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52, Week 54, Week 58

Outcome Measure Data

Analysis Population Description

Data for the number of step-up and step-down changes in classification of asthma severity by medication usage were not tabulated or analyzed as accurate dose information data for all concomitant medications were not available due to inconsistencies in the way concomitant medication data were collected.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	0	0

16. Secondary Outcome

Title	Step Classification of Asthma Severity by Medication Usage
Description	Step classification of asthma severity by medication usage. Subjects were classified at each visit according to the medication used on the day of the particular time-point; Step 1: intermittent asthma, Step 2: mild persistent asthma, Step 3: moderate persistent asthma, Step 4: severe persistent asthma. The number (%) of subjects in each step classification were provided at each assessment timepoint with a shift table indicating the number (%) of subjects moving from each step classification at each time-point.
Time Frame	Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52, Week 54, Week 58

Outcome Measure Data

Analysis Population Description

Data for step classification of asthma severity by medication usage were not tabulated or analyzed as accurate dose information data for all concomitant medications were not available due to inconsistencies in the way concomitant medication data were collected.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	0	0

17. Secondary Outcome

Title	Mean Weekly Asthma Symptom Scores
Description	Mean weekly asthma symptom scores: subjects recorded their asthma symptom scores in an electronic symptom diary twice daily throughout the study, immediately upon awakening (5-10 AM) and in the evening or at bedtime (7-12 PM). Questions included extent of albuterol use, symptoms of wheezing, coughing, activity limitations and sleep; scale 0 (none/fine) to 3 (severe/ continuous/bad night).
Time Frame	Baseline through end of study

Outcome Measure Data

Analysis Population Description

Data for mean weekly asthma symptom scores were not presented due to lack of resource resulting from scaling down of Exubera® (inhaled insulin) development.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	0	0

18. Secondary Outcome

Title	Incidence of Non-severe Asthma Exacerbations
Description	Non-severe asthma exacerbation = one of the following: any home monitored morning (4:45 am - 10:15 am) forced expiratory volume in 1 second (FEV1) <80% of the morning baseline for 2 or more consecutive days; or home monitored FEV1 <60% of Baseline at any time. Percent of Baseline = 100*(daily FEV1)/Baseline weekly FEV1. Subject-months=elapsed number of months a subject was in the study in each time interval. Crude event rate = total events divided by subject-months.
Time Frame	0 to 1 week to > 12 months

Outcome Measure Data

Analysis Population Description

FAS; review of source data for this endpoint showed excessive data variability for home-monitored FEV1 with outliers ranging from 0.01 to >100, and many subjects with random peaks and dips of 100% or more of their baseline. It is unlikely that the protocol definition is robust enough to provide real information about exacerbation frequencies.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
0 to 1 Week (n=141, 139)	0.43	0.41
>1 to 2 Weeks (n=141, 139)	0.28	0.38
>2 to 3 Weeks (n=141, 139)	0.22	0.31
>3 to 4 Weeks (n=141, 139)	0.37	0.41
>4 to 6 Weeks (n=141, 139)	0.52	0.36
>6 to 9 Weeks (n=138, 139)	0.53	0.51
>9 to 12 Weeks (n=134, 138)	0.35	0.46
>3 Months (n=133, 137)	0.40	0.40
>6 to 9 Months (n=121, 133)	0.30	0.49
>9 to 12 Months (n=114, 131)	0.27	0.43
>12 Months (n=67, 81)	0.34	0.21
Overall (n=141, 139)	0.35	0.43

19. Secondary Outcome

Title	Incidence of Severe Asthma Exacerbations
Description	Severe asthma exacerbation was defined as one of the following: subject received oral (systemic) corticosteriods for the treatment of asthma; or subject had an unscheduled visit to a physician, emergency room, or hospital for the treatment of asthma. Subject-months=elapsed number of months a subject was in the study in each time interval. Crude event rate = total events divided by subject-months * 100.
Time Frame	0 to 1 Week to > 12 Months

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); due to inconsistencies in data entry for systemic steroids, the protocol definition for severe asthma exacerbations, which was based on systemic corticosteroid use for asthma, could not be accurately assessed. Due the small number of events the incidence of severe asthma exacerbations was assessed per 100 months.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
0 to 1 Week (n=141, 139)	0.00	0.00
>1 to 2 Weeks (n=141, 139)	0.00	3.13
>2 to 3 Weeks (n=141, 139)	0.00	9.39
>3 to 4 Weeks (n=141, 139)	3.08	0.00
>4 to 6 Weeks (n=141, 139)	4.63	1.56
>6 to 9 Weeks (n=138, 139)	1.06	0.00
>9 to 12 Weeks (n=134, 138)	1.09	0.00
>3 Months (n=133, 137)	1.20	2.27
>6 to 9 Months (n=121, 133)	1.43	1.01
>9 to 12 Months (n=114, 131)	1.53	1.33
>12 Months (n=67, 81)	3.39	0.00
Overall (n=141, 139)	1.46	1.47

20. Secondary Outcome

Title	Number of Systemic Corticosteroid Rescues
Description	Number of subjects who used a systemic corticosteroid at any time during the study, and the total number of systemic corticosteroid rescues. New rescue event = >=2 consecutive days between the end of one event and the start of another event.
Time Frame	Baseline through Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); number of subjects with systemic corticosteroid rescues = inhaled insulin: 12, and subcutaneous insulin: 14. Due to inconsistencies in data entry, the numbers of systemic corticosteroid rescues were not considered entirely accurate.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
Number [systemic corticosteriod rescues]	14	16

21. Primary Outcome

Title	Annualized Rate of Change for Hemoglobin-adjusted Carbon Monoxide Diffusion Capacity (DLco)
Description	Annualized rates of change (slope throughout time from baseline to end of study[visit]) for hemoglobin-adjusted carbon monoxide diffusion capacity (DLco)in milliliters per minute/millimeters of mercury/year (ml/min/mmHg/yr) measured 30 minutes following the administration of albuterol.
Time Frame	Weeks -3, -2, -1, 1, 2, 3, 4, 6, 12, 18, 26, 39, and 52

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS).

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	117	127
Mean (Standard Error) [ml/min/mmHg/yr]	-0.776 (0.152)	-0.273 (0.153)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Treatment group difference (Exubera minus subcutaneous insulin): annualized rate of change over time. Longitudinal data analysis methods with random effects were used to model the pulmonary function test (PFT) measurements. Random effects included the intercept and slope with respect to time (visit); all remaining effects were fixed. The estimated rate of change over time for each treatment group was derived from this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.503
	Confidence Interval	() 90%; -0.858 to -0.148
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.216
	Estimation Comments	Primary analysis model includes terms of Treatment, Time, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on day of randomization.

22. Secondary Outcome

Title	Asthma Control as Measured by the Asthma Control Questionnaire©
Description	Asthma Control Questionnaire©: 6 self-administered questions that assess asthma control over the past week covering nocturnal waking, morning symptoms, activity limitations, shortness of breath, wheezing, and short-acting bronchodilator use; 7-point ordinal rating scale from 0 (good control) to 6 (poor control). A seventh question was completed by a health professional on forced expiratory volume in 1 second (FEV1) % predicted using a one-week recall period; scale: 0 (>95% predicted) to 6 (<50% predicted). Overall score = mean of questions 1 - 7.
Time Frame	Baseline, Weeks 4, 12, 26, 39, 52

Outcome Measure Data

Analysis Population Description

FAS; abbreviations: Eval = evaluations, BL = Baseline.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	138	138
Baseline: Subject Evaluation (n=138, 138)	1.04 (0.78)	1.21 (0.91)
Baseline: Clinical Evaluation (n=138, 138)	2.50 (1.50)	2.54 (1.70)
Baseline: Overall Evaluation (n=138, 138)	1.25 (0.74)	1.40 (0.86)
Week 4: Subject Evaluation (n=123, 121)	1.08 (0.81)	1.15 (0.89)
Week 4: Clinical Evaluation (n=123, 121)	2.68 (1.52)	2.65 (1.61)
Week 4: Overall Evaluation (n=123, 121)	1.31 (0.78)	1.36 (0.81)
Week 12: Subject Evaluation (n=129, 134)	1.04 (0.83)	1.17 (0.91)
Week 12: Clinical Evaluation (n=129, 134)	2.55 (1.50)	2.61 (1.48)
Week 12: Overall Evaluation (n=129, 134)	1.25 (0.77)	1.37 (0.83)
Week 26: Subject Evaluation (n=121, 131)	1.06 (0.80)	1.07 (0.91)
Week 26: Clinical Evaluation (n=121, 131)	2.48 (1.43)	2.61 (1.57)
Week 26: Overall Evaluation (n=121, 131)	1.27 (0.74)	1.29 (0.85)
Week 39: Subject Evaluation (n=110, 125)	0.94 (0.76)	1.00 (0.85)
Week 39: Clinical Evaluation (n=110, 125)	2.54 (1.43)	2.63 (1.52)
Week 39: Overall Evaluation (n=110, 125)	1.17 (0.71)	1.23 (0.81)
Week 52: Subject Evaluation (n=107, 120)	1.08 (1.07)	0.98 (0.84)
Week 52: Clinical Evaluation (n=107, 120)	2.77 (1.54)	2.64 (1.56)
Week 52: Overall Evaluation (n=107, 120)	1.32 (0.99)	1.21 (0.80)
Week 4: Subject Eval: Change from BL (n=122, 120)	0.02 (0.59)	-0.07 (0.59)
Week 4: Clinical Eval: Change from BL (n=122, 120)	0.17 (0.85)	0.14 (0.85)
Week 4: Overall Eval: Change from BL (n=122, 120)	0.04 (0.55)	-0.04 (0.53)
Week 12: Subject Eval: Change from BL (n=129, 134)	-0.02 (0.66)	-0.04 (0.72)
Week 12 Clinical Eval: Change from BL (n=129, 134)	0.12 (0.94)	0.09 (0.91)
Week 12: Overall Eval: Change from BL (n=129, 134)	0.00 (0.59)	-0.02 (0.62)
Week 26: Subject Eval: Change from BL (n=121, 130)	0.05 (0.77)	-0.12 (0.82)
Week 26 Clinical Eval: Change from BL (n=121, 130)	0.09 (0.78)	0.09 (1.00)
Week 26: Overall Eval: Change from BL (n=121, 130)	0.05 (0.68)	-0.09 (0.73)
Week 39: Subject Eval: Change from BL (n=110, 124)	-0.09 (0.65)	-0.19 (0.77)
Week 39 Clinical Eval: Change from BL (n=110, 124)	0.14 (1.05)	0.11 (0.94)
Week 39: Overall Eval: Change from BL (n=110, 124)	-0.06 (0.58)	-0.15 (0.68)
Week 52: Subject Eval: Change from BL (n=106, 119)	0.06 (0.88)	-0.19 (0.86)
Week 52 Clinical Eval: Change from BL (n=106, 119)	0.38 (0.87)	0.10 (1.20)
Week 52: Overall Eval: Change from BL (n=106, 119)	0.11 (0.77)	-0.15 (0.77)

23. Secondary Outcome

Title	Baseline Dyspnea Index (BDI)
Description	Total score = the sum of the numeric grades from the three dyspnea index questions. Functional Impairment rating scale: Grade 4 (no impairment) to Grade 0 (very severe impairment); Magnitude of Task rating scale: Grade 4 (extraordinary) to Grade 0 (no task); and Magnitude of Effort rating scale: Grade 4 (extraordinary) to grade 0 (no effort).
Time Frame	run-in period

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	139	138
Functional Impairment	3.37 (0.80)	3.36 (0.87)
Magnitude of Task	2.29 (1.19)	2.29 (1.25)
Magnitude of Effort	2.49 (1.39)	2.34 (1.49)
Total Score	8.15 (2.98)	7.97 (2.99)

24. Secondary Outcome

Title	Transition Dyspnea Index (TDI): Change in Total Score
Description	Transition Dyspnea Index total score = sum of the numeric grades from the three dyspnea index questions: Change in Functional Impairment, Change in Magnitude of Task, and Change in Magnitude of Effort. Rating scale: -3 (major deterioration), -2 (moderate deterioration), -1 (minor deterioration, 0 (no change), +1 (minor improvement), +2 (moderate improvement), +3 (major improvement).
Time Frame	Week 4, Week 12, Week 26, Week 39, Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	131	135
Week 4 (n=121, 122)	0.36 (1.93)	0.50 (1.92)
Week 12 (n=131, 135)	0.51 (1.76)	0.47 (1.68)
Week 26 (n=124, 131)	0.14 (1.75)	0.13 (1.55)
Week 39 (n=112, 127)	0.26 (1.56)	0.29 (1.61)
Week 52 (n=105, 121)	0.13 (1.65)	0.67 (2.01)

25. Secondary Outcome

Title	Glycosylated Hemoglobin (HbA1c)
Description	Glycosylated Hemoglobin (HbA1c): observed mean values at Baseline and each observation, and change from Baseline. Change from Baseline = mean HbA1c at observation minus mean HbA1c at Baseline.
Time Frame	Baseline, Week 6, Week 12, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	135	135
Baseline (n=135, 135)	7.62 (1.12)	7.43 (1.08)
Week 6: Observed Value (n=127, 126)	7.22 (1.00)	6.97 (0.90)
Week 6: Change from Baseline (n=127, 126)	-0.38 (0.65)	-0.43 (0.49)
Week 12: Observed Value (n=122, 127)	7.28 (1.12)	6.98 (0.97)
Week 12: Change from Baseline (n=122, 127)	-0.32 (0.98)	-0.48 (0.69)
Week 26: Observed Value (n=118, 120)	7.38 (1.24)	7.19 (1.18)
Week 26: Change from Baseline (n=118, 120)	-0.12 (1.07)	-0.25 (0.93)
Week 39: Observed Value (n=108, 123)	7.44 (1.31)	7.20 (1.16)
Week 39: Change from Baseline (n=108, 123)	-0.08 (1.10)	-0.21 (0.91)
Week 52: Observed Value (n=101, 118)	7.51 (1.35)	7.35 (1.28)
Week 52: Change from Baseline (n=101, 118)	0.00 (1.05)	-0.05 (1.01)
Week 52 (LOCF): Observed Value (n=135, 135)	7.58 (1.35)	7.40 (1.36)
Week 52 (LOCF): Change from Baseline (n=135, 135)	-0.04 (1.07)	-0.03 (1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of treatment, Week, Baseline HbA1c, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.11
	Confidence Interval	() 90%; -0.06 to 0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of treatment, Week, Baseline HbA1c, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.21
	Confidence Interval	() 90%; 0.04 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of treatment, Week, Baseline HbA1c, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	() 90%; -0.01 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of treatment, Week, Baseline HbA1c, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.14
	Confidence Interval	() 90%; -0.03 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of treatment, Week, Baseline HbA1c, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.06
	Confidence Interval	() 90%; -0.12 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52 (LOCF); Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of treatment, Week, Baseline HbA1c, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	() 90%; -0.19 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

26. Secondary Outcome

Title	Fasting Plasma Glucose
Description	Fasting plasma glucose (milligrams per deciliter [mg/dL]) at Baseline, and change from Baseline. Change from baseline: mean of value of fasting plasma glucose in mg/dL at observation minus baseline value.
Time Frame	Baseline, Week 6, Week 12, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS); Last Observation Carried Forward: if the end of study value was missing the last available observation for that subject was used..

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	112	123
Baseline (n=112, 123)	149.22 (49.92)	149.03 (58.33)
Week 6: Observed Value (n=103, 112)	143.02 (68.92)	136.54 (57.98)
Week 6: Change from Baseline (n=103, 112)	-3.34 (68.47)	-15.19 (67.16)
Week 12: Observed Value (n=106, 113)	136.32 (63.00)	144.47 (61.22)
Week 12: Change from Baseline (n=106, 113)	-12.16 (65.62)	-5.40 (67.71)
Week 26: Observed Value (n=102, 114)	139.05 (64.63)	143.54 (52.09)
Week 26: Change from Baseline (n=102, 114)	-11.86 (76.07)	-4.63 (65.10)
Week 39: Observed Value (n=102, 115)	143.64 (63.89)	142.91 (66.26)
Week 39: Change from Baseline (n=102, 115)	-5.67 (67.65)	-7.47 (65.55)
Week 52: Observed Value (n=98, 115)	146.32 (66.04)	145.43 (59.35)
Week 52: Change from Baseline (n=98, 115)	-3.86 (60.61)	-2.53 (63.23)
Week 52 LOCF: Observed Value (n=112, 123)	148.28 (71.07)	144.96 (58.80)
Week 52 LOCF: Change from Baseline (n=112, 123)	-0.95 (72.53)	-4.07 (62.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; Analysis of change from Baseline in fasting plasma glucose: Inhaled Insulin - Subcutaneouas Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline, Fasting Plasma Glucose, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.615
	Confidence Interval	() 90%; -2.351 to 23.581
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.874
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; Analysis of change from Baseline in fasting plasma glucose: Inhaled Insulin - Subcutaneouas Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline, Fasting Plasma Glucose, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.942
	Confidence Interval	() 90%; -19.79 to 5.909
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.804
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; Analysis of change from Baseline in fasting plasma glucose: Inhaled Insulin - Subcutaneouas Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline, Fasting Plasma Glucose, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.622
	Confidence Interval	() 90%; -17.63 to 8.382
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.897
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; Analysis of change from Baseline in fasting plasma glucose: Inhaled Insulin - Subcutaneouas Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline, Fasting Plasma Glucose, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.828
	Confidence Interval	() 90%; -11.16 to 14.817
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.888
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; Analysis of change from Baseline in fasting plasma glucose: Inhaled Insulin - Subcutaneouas Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline, Fasting Plasma Glucose, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.149
	Confidence Interval	() 90%; -12.01 to 14.307
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.991
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52 (LOCF); Analysis of change from Baseline in fasting plasma glucose: Inhaled Insulin - Subcutaneouas Insulin. Adjusted (Primary Analysis Model): includes terms of Treatment, Week, Baseline, Fasting Plasma Glucose, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.247
	Confidence Interval	() 90%; -8.664 to 17.157
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.816
	Estimation Comments

27. Secondary Outcome

Title	Body Weight: Mean Baseline and Change From Baseline
Description	Body weight: mean Baseline and change from Baseline in kilograms (kg). Change from baseline = mean body weight in kilograms (kg) at observation minus baseline value.
Time Frame	Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 11, Week 12, Week 18, Wek 26, Week 39, Week 50, Week 51, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS)

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	113	124
Baseline (n=113, 124)	87.41 (21.04)	87.13 (17.58)
Week 1: Change from Baseline (n=102, 113)	-0.02 (1.45)	1.00 (7.63)
Week 2: Change from Baseline (n=104, 105)	0.12 (1.31)	0.57 (1.50)
Week 3: Change from Baseline (n=103, 113)	0.18 (1.64)	0.34 (1.55)
Week 4: Change from Baseline (n=101, 119)	0.31 (1.74)	0.44 (1.70)
Week 6: Change from Baseline (n=106, 122)	0.13 (1.93)	0.68 (1.88)
Week 9: Change from Baseline (n=101, 104)	0.14 (2.31)	0.91 (2.33)
Week 11: Change from Baseline (n=14, 17)	0.71 (1.77)	0.69 (2.00)
Week 12: Change from Baseline (n=106, 118)	0.01 (2.96)	0.84 (2.83)
Week 18: Change from Baseline (n=110, 116)	0.35 (3.04)	1.27 (3.46)
Week 26: Change from Baseline (n=111, 121)	0.72 (3.52)	1.29 (3.32)
Week 39: Change from Baseline (n=107, 121)	0.77 (4.33)	1.33 (3.70)
Week 50: Change from Baseline (n=19, 13)	0.04 (3.67)	1.98 (3.90)
Week 51: Change from Baseline (n=49, 60)	0.24 (3.75)	0.63 (4.38)
Week 52: Change from Baseline (n=90, 109)	1.34 (3.98)	1.26 (4.08)
Week 52 LOCF: Change from Baseline (n=113, 124)	1.13 (3.95)	1.44 (4.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 1; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.080
	Confidence Interval	() 90%; -1.829 to -0.331
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.455
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 2; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.475
	Confidence Interval	() 90%; -1.233 to 0.284
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.461
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 3; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.185
	Confidence Interval	() 90%; -0.931 to 0.562
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.454
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 4; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.189
	Confidence Interval	() 90%; -0.929 to 0.550
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.449
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.558
	Confidence Interval	() 90%; -1.294 to 0.178
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.447
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 9; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.748
	Confidence Interval	() 90%; -1.517 to 0.022
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.467
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 11; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.053
	Confidence Interval	() 90%; -2.510 to 0.405
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.886
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.891
	Confidence Interval	() 90%; -1.634 to -0.149
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.451
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 18; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.980
	Confidence Interval	() 90%; -1.725 to -0.234
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.453
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.663
	Confidence Interval	() 90%; -1.400 to 0.075
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.448
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.537
	Confidence Interval	() 90%; -1.279 to 0.205
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.451
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 50; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.322
	Confidence Interval	() 90%; -3.012 to 0.369
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.027
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 51; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.063
	Confidence Interval	() 90%; -0.847 to 0.972
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.552
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.193
	Confidence Interval	() 90%; -0.964 to 0.579
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.469
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52 (LOCF); adjusted mean difference between inhaled insulin and subcutaneous insulin groups. Primary analysis model includes terms of Treatment, Week, Baseline Body Weight, Center, and Type of Diabetes.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.430
	Confidence Interval	() 90%; -1.298 to 0.438
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.526
	Estimation Comments

28. Secondary Outcome

Title	Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight)
Description	Total Daily Long-Acting Insulin Dose Unadjusted for Body Weight: long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. Inhaled Insulin reported in mg. Subcutaneous Insulin reported in units.
Time Frame	Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS)

Arm/Group Title	Inhaled Insulin (mg)	Subcutaneous Insulin (Units)
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	111	122
Baseline (n=105, 121)	41.70 (24.61)	45.50 (27.54)
Week 1 (n=104, 117)	41.75 (25.75)	45.46 (28.69)
Week 2 (n=106, 111)	43.48 (26.76)	47.19 (28.08)
Week 3 (n=104, 117)	43.75 (27.32)	47.61 (29.06)
Week 4 (n=104, 120)	44.70 (28.06)	48.54 (29.91)
Week 6 (n=106, 122)	45.89 (29.31)	48.59 (30.68)
Week 9 (n=104, 109)	46.01 (30.57)	47.68 (29.16)
Week 12 (n=110, 122)	46.05 (30.82)	49.04 (30.99)
Week 18 (n=110, 120)	47.15 (32.34)	49.94 (30.95)
Week 26 (n=111, 122)	47.65 (33.87)	49.98 (31.32)
Week 39 (n=107, 121)	48.97 (33.28)	50.32 (31.58)
Week 52 (n=101, 119)	50.17 (34.17)	50.07 (31.62)

29. Secondary Outcome

Title	Total Daily Long-Acting Insulin Dose Adjusted for Body Weight
Description	Total daily dose of long-acting insulin adjusted for body weight (units per kilogram [kg]). Long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. Inhaled Insulin reported in mg/kg. Subcutaneous Insulin reported in units/kg.
Time Frame	Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS)

Arm/Group Title	Inhaled Insulin (mg/kg)	Subcutaneous Insulin (Units/kg)
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	109	121
Baseline (n=105, 121)	0.47 (0.25)	0.52 (0.30)
Week 1 (n=100, 112)	0.47 (0.27)	0.53 (0.31)
Week 2 (n=103, 104)	0.49 (0.29)	0.52 (0.28)
Week 3 (n=101, 113)	0.49 (0.29)	0.54 (0.31)
Week 4 (n=99, 118)	0.49 (0.27)	0.54 (0.31)
Week 6 (n=104, 121)	0.52 (0.31)	0.55 (0.32)
Week 9 (n=99, 103)	0.51 (0.31)	0.54 (0.32)
Week 12 (n=104, 117)	0.52 (0.32)	0.55 (0.32)
Week 18 (n=108, 115)	0.53 (0.33)	0.55 (0.32)
Week 26 (n=109, 120)	0.52 (0.33)	0.55 (0.32)
Week 39 (n=105, 120)	0.54 (0.37)	0.56 (0.32)
Week 52 (n=88, 108)	0.53 (0.36)	0.55 (0.31)

30. Secondary Outcome

Title	Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Description	Average Total Daily Insulin Dose: short-acting insulin (milligrams [mg]). 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.
Time Frame	Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS)

Arm/Group Title	Inhaled Insulin (mg)	Subcutaneous Insulin (Units)
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	113	141
Baseline (n=109, 122)	30.56 (22.69)	30.74 (19.50)
Week 1 (n=106, 118)	11.03 (5.51)	29.52 (19.95)
Week 2 (n=108, 111)	12.13 (6.03)	31.24 (21.69)
Week 3 (n=106, 116)	12.96 (6.68)	30.58 (20.70)
Week 4 (n=106, 120)	13.44 (6.82)	31.87 (22.23)
Week 6 (n=108, 122)	14.04 (7.06)	31.81 (21.94)
Week 9 (n=106, 110)	14.03 (7.76)	31.55 (23.93)
Week 12 (n=112, 122)	14.42 (8.11)	32.71 (23.70)
Week 18 (n=112, 120)	15.11 (8.68)	33.49 (23.81)
Week 26 (n=113, 122)	15.95 (9.14)	33.80 (24.37)
Week 39 (n=109, 121)	16.17 (10.25)	33.12 (24.62)
Week 52 (n= 103, 119)	17.20 (10.95)	33.04 (26.09)

31. Secondary Outcome

Title	Total Daily Short-Acting Insulin Dose Adjusted for Body Weight
Description	Total Daily Short-Acting Insulin Dose adjusted for body weight (units divided by 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.
Time Frame	Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12, Week 18, Week 26, Week 39, Week 52

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS)

Arm/Group Title	Inhaled Insulin (mg/kg)	Subcutaneous Insulin (Units/kg)
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	111	122
Baseline (n=109, 122)	0.35 (0.25)	0.36 (0.22)
Week 1 (n=102, 113)	0.12 (0.06)	0.34 (0.23)
Week 2 (n=104, 104)	0.14 (0.07)	0.36 (0.25)
Week 3 (n=103, 112)	0.15 (0.07)	0.35 (0.23)
Week 4 (n=101, 118)	0.15 (0.07)	0.37 (0.26)
Week 6 (n=106, 121)	0.16 (0.08)	0.36 (0.24)
Week 9 (n=101, 104)	0.16 (0.09)	0.36 (0.26)
Week 12 (n=106, 117)	0.16 (0.08)	0.38 (0.26)
Week 18 (n=110, 116)	0.18 (0.10)	0.37 (0.25)
Week 26 (n=111, 121)	0.19 (0.11)	0.38 (0.27)
Week 39 (n=107, 120)	0.19 (0.12)	0.38 (0.27)
Week 52 (n=90, 108)	0.19 (0.12)	0.36 (0.29)

32. Secondary Outcome

Title	Lipids: Median Change From Baseline to Last Observation
Description	Lipids: median changes (milligrams per deciliter [mg/dL]) from Baseline median to last observation in cholesterol (random), triglycerides (random), high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol. Normalized data was used in the computations. Last observation = last observation while on study drug or during the lag. Measures of dispersion for median changes in lipids were not determined.
Time Frame	Baseline to Last Observation

Outcome Measure Data

Analysis Population Description

Primary analysis set (PAS); median change from Baseline to last observation. Last observation was defined as last observation while on study drug or during the lag. Full range (-999 to 999) was not calculated.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	110	121
Cholesterol (random) (n=110, 121)	-0.5 (-0.5)	0 (0)
Triglycerides (random) (n=105, 121)	9 (9)	-8 (-8)
HDL Cholesterol (n=110, 121)	-3 (-3)	1 (1)
LDL Cholesterol (n=97, 110)	0 (0)	0 (0)

33. Secondary Outcome

Title	Hypoglycemic Event Rates
Description	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. Crude event rate = total events divided by subject months. Subject months = elapsed number of months a subject was in the study in each time interval.
Time Frame	0 to 1 month to 11 to 12 months, and Overall

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	135	135
0 to 1 month (n=135, 135)	2.99	2.48
> 1 to 2 months (n=135, 135)	2.52	2.34
> 2 to 3 months (n=131, 134)	2.12	1.84
> 3 to 4 months (n=128, 134)	1.84	1.61
> 4 to 5 months (n=126, 134)	1.94	1.69
> 5 to 6 months (n=121, 131)	1.51	1.84
> 6 to 7 months (n=119, 131)	1.50	1.67
> 7 to 8 months (n=115, 129)	1.45	1.26
> 8 to 9 months (n=111, 129)	1.62	1.26
> 9 to 10 months (n=110, 129)	1.26	1.55
> 10 to 11 months (n=109, 125)	1.12	1.37
> 11 to 12 months (n=104, 123)	1.18	1.23
Overall (n=135, 135)	1.79	1.68

34. Secondary Outcome

Title	Severe Hypoglycemic Event Rates
Description	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); blood glucose measurement was ≤ 49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, subcutaneous glucagon, or i.v. glucose. Crude event rate = number of events divided by 100 subject-months. Subject months = elapsed number of months subject was in study in each time interval.
Time Frame	0 to 1 month to 11 to 12 months, and Overall

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS). Due the small number of events severe hypoglycemic event rates were assessed per 100 months.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	135	135
0 to 1 month (n=135, 135)	2.91	1.48
> 1 to 2 months (n=135, 135)	5.22	1.49
> 2 to 3 months (n=131, 134)	4.64	2.99
> 3 to 4 months (n=128, 134)	0.78	2.24
> 4 to 5 months (n=126, 134)	4.05	1.51
> 5 to 6 months (n=121, 131)	3.33	2.29
> 6 to 7 months (n=119, 131)	0.00	0.77
> 7 to 8 months (n=115, 129)	0.89	2.33
> 8 to 9 months (n=111, 129)	5.42	1.55
> 9 to 10 months (n=110, 129)	0.91	3.18
> 10 to 11 months (n=109, 125)	1.88	2.41
> 11 to 12 months (n=104, 123)	3.95	3.10
Overall (n=135, 135)	2.89	2.13

35. Primary Outcome

Title	Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second (FEV1)
Description	Change from Baseline at each visit in post-bronchodilator forced expiratory volume in one second (FEV1). FEV1 was measured in liters (L) 30 minutes following the administration of albuterol. Change from baseline: mean FEV1 (L) at observation minus baseline value.
Time Frame	Baseline through Week 52 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): all subjects who were randomized, had a baseline post-albuterol pulmonary function test (PFT) measurement, and had at least two post-baseline, post-albuterol PFT measurements. LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
Baseline (n=141, 139)	2.559 (0.771)	2.524 (0.742)
Week 1 (n=123, 125)	-0.066 (0.150)	-0.027 (0.126)
Week 2 (n=126, 115)	-0.056 (0.150)	-0.031 (0.128)
Week 3 (n=131, 119)	-0.077 (0.185)	-0.030 (0.130)
Week 4 (n=121, 129)	-0.074 (0.161)	-0.022 (0.155)
Week 6 (n=130, 135)	-0.070 (0.248)	-0.025 (0.146)
Week 12 (n=125, 129)	-0.053 (0.212)	-0.031 (0.182)
Week 18 (n=124, 125)	-0.066 (0.226)	-0.040 (0.165)
Week 26 (n=120, 128)	-0.056 (0.175)	-0.038 (0.184)
Week 39 (n=107, 124)	-0.088 (0.191)	-0.039 (0.194)
Week 52 (n=106, 112)	-0.131 (0.259)	-0.059 (0.234)
Week 52 LOCF (n=141, 139)	-0.113 (0.261)	-0.062 (0.225)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 1; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.039
	Confidence Interval	() 90%; -0.079 to -0.000
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 2; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.029
	Confidence Interval	() 90%; -0.068 to 0.010
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 3; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.045
	Confidence Interval	() 90%; -0.084 to -0.006
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 4; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.046
	Confidence Interval	() 90%; -0.085 to -0.007
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.046
	Confidence Interval	() 90%; -0.085 to -0.007
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.023
	Confidence Interval	() 90%; -0.063 to 0.017
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.024
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 18; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.021
	Confidence Interval	() 90%; -0.062 to 0.020
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.025
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.014
	Confidence Interval	() 90%; -0.055 to 0.027
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.025
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.042
	Confidence Interval	() 90%; -0.085 to 0.000
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.026
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.065
	Confidence Interval	() 90%; -0.109 to -0.022
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.027
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52 Last Observation Carried Forward (LOCF; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.050
	Confidence Interval	() 90%; -0.097 to -0.003
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.028
	Estimation Comments

36. Primary Outcome

Title	Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusing Capacity (DLco)
Description	Carbon Monoxide Diffusing Capacity (DLco) measured in milliters/minutes/millimeters of mercury (mL/min/mmHg) 30 minutes following the administration of albuterol. Change from Baseline: mean DLco (mL/min/mmHg) at observation minus baseline value.
Time Frame	Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 12, Week 18, Week 26, Week 39, Week 52, Week 52 Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS); LOCF: last observation carried forward.

Arm/Group Title	Inhaled Insulin	Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.	Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
Measure Participants	141	139
Baseline (n=141, 139)	23.023 (5.914)	22.883 (6.079)
Week 1 (n=122, 124)	-0.574 (1.392)	-0.333 (1.405)
Week 2 (n=126, 112)	-0.777 (1.631)	-0.481 (1.290)
Week 3 (n=129, 118)	-0.811 (1.244)	-0.506 (1.388)
Week 4 (n=120, 128)	-1.075 (1.425)	-0.576 (1.397)
Week 6 (n=129, 135)	-1.017 (1.633)	-0.602 (1.488)
Week 12 (n=125, 125)	-0.961 (1.738)	-0.477 (1.588)
Week 18 (n=124, 123)	-1.024 (1.774)	-0.549 (1.601)
Week 26 (n=119, 127)	-0.849 (1.914)	-0.477 (1.706)
Week 39 (n=107, 123)	-1.016 (1.649)	-0.395 (1.767)
Week 52 (n=105, 110)	-1.483 (1.944)	-0.798 (1.967)
Week 52 LOCF (n=141, 139)	-1.426 (1.856)	-0.682 (1.958)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 1; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.279
	Confidence Interval	() 90%; -0.606 to 0.048
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.199
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 2; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.336
	Confidence Interval	() 90%; -0.661 to -0.011
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.198
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 3; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.384
	Confidence Interval	() 90%; -0.707 to -0.061
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.196
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 4; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.516
	Confidence Interval	() 90%; -0.842 to -0.191
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.198
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 6; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.474
	Confidence Interval	() 90%; -0.797 to -0.152
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.196
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 12; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.533
	Confidence Interval	() 90%; -0.866 to -0.200
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.202
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 18; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.509
	Confidence Interval	() 90%; -0.845 to -0.174
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.204
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 26; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.412
	Confidence Interval	() 90%; -0.749 to -0.076
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.204
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 39; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.707
	Confidence Interval	() 90%; -1.056 to -0.358
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.212
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52; Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.680
	Confidence Interval	() 90%; -1.040 to -0.320
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.219
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin, Subcutaneous Insulin
	Comments	Week 52 Last Observation Carried Forward (LOCF); Inhaled Insulin - Subcutaneous Insulin. Adjusted (primary analysis model) includes terms of Treatment, Week, Baseline pulmonary function test (PFT), Center, Age, Sex, Baseline Height, Type of Diabetes, and Controller Medications Use on Day of Randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.765
	Confidence Interval	() 90%; -1.116 to -0.415
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.212
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	Adverse events for this study are reported using MedDRA in these Basic Results, but are reported using COSTART in the Clinical Study Report and PhRMA Web Synopsis for consistency with earlier studies. Consequently, subtle differences may be observed.
Arm/Group Title	Inhaled Insulin		Subcutaneous Insulin
Arm/Group Description	Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin.		Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
All Cause Mortality
	Inhaled Insulin		Subcutaneous Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Inhaled Insulin		Subcutaneous Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/146 (14.4%)		13/141 (9.2%)
Blood and lymphatic system disorders
Haemorrhagic anaemia	1/146 (0.7%)		0/141 (0%)
Cardiac disorders
Acute coronary syndrome	0/146 (0%)		2/141 (1.4%)
Angina pectoris	1/146 (0.7%)		0/141 (0%)
Angina unstable	1/146 (0.7%)		0/141 (0%)
Arteriosclerosis coronary artery	1/146 (0.7%)		0/141 (0%)
Atrial fibrillation	0/146 (0%)		1/141 (0.7%)
Atrial flutter	0/146 (0%)		1/141 (0.7%)
Atrioventricular block	1/146 (0.7%)		0/141 (0%)
Myocardial infarction	0/146 (0%)		1/141 (0.7%)
Gastrointestinal disorders
Hiatus hernia	1/146 (0.7%)		0/141 (0%)
Small intestinal obstruction	1/146 (0.7%)		0/141 (0%)
Upper gastrointestinal haemorrhage	1/146 (0.7%)		0/141 (0%)
General disorders
Chest pain	2/146 (1.4%)		1/141 (0.7%)
Hepatobiliary disorders
Hepatitis alcoholic	1/146 (0.7%)		0/141 (0%)
Infections and infestations
Abdominal wall abscess	0/146 (0%)		1/141 (0.7%)
Erysipelas	1/146 (0.7%)		0/141 (0%)
Gastroenteritis	1/146 (0.7%)		0/141 (0%)
Pneumonia	0/146 (0%)		1/141 (0.7%)
Viral infection	1/146 (0.7%)		0/141 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/146 (0.7%)		0/141 (0%)
Hyperglycaemia	0/146 (0%)		1/141 (0.7%)
Hypoglycaemia	3/146 (2.1%)		0/141 (0%)
Ketoacidosis	1/146 (0.7%)		0/141 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	1/146 (0.7%)		0/141 (0%)
Intervertebral disc protrusion	1/146 (0.7%)		1/141 (0.7%)
Lumbar spinal stenosis	0/146 (0%)		1/141 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma	1/146 (0.7%)		0/141 (0%)
Lymphoma	0/146 (0%)		1/141 (0.7%)
Nervous system disorders
Cerebrovascular accident	1/146 (0.7%)		0/141 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/146 (0.7%)		0/141 (0%)
Psychiatric disorders
Alcohol abuse	1/146 (0.7%)		0/141 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	3/146 (2.1%)		2/141 (1.4%)
Cough	0/146 (0%)		1/141 (0.7%)
Pleural effusion	0/146 (0%)		1/141 (0.7%)
Other (Not Including Serious) Adverse Events
	Inhaled Insulin		Subcutaneous Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/146 (95.9%)		136/141 (96.5%)
Eye disorders
Conjunctivitis	3/146 (2.1%)		9/141 (6.4%)
Gastrointestinal disorders
Constipation	4/146 (2.7%)		8/141 (5.7%)
Diarrhoea	10/146 (6.8%)		6/141 (4.3%)
Nausea	12/146 (8.2%)		8/141 (5.7%)
Vomiting	8/146 (5.5%)		5/141 (3.5%)
General disorders
Chest pain	8/146 (5.5%)		7/141 (5%)
Fatigue	9/146 (6.2%)		7/141 (5%)
Oedema peripheral	11/146 (7.5%)		14/141 (9.9%)
Immune system disorders
Seasonal allergy	3/146 (2.1%)		7/141 (5%)
Infections and infestations
Bronchitis	24/146 (16.4%)		18/141 (12.8%)
Gastroenteritis	8/146 (5.5%)		7/141 (5%)
Gastroenteritis viral	5/146 (3.4%)		7/141 (5%)
Influenza	20/146 (13.7%)		25/141 (17.7%)
Nasopharyngitis	29/146 (19.9%)		26/141 (18.4%)
Sinusitis	14/146 (9.6%)		21/141 (14.9%)
Upper respiratory tract infection	44/146 (30.1%)		39/141 (27.7%)
Urinary tract infection	18/146 (12.3%)		20/141 (14.2%)
Metabolism and nutrition disorders
Hypoglycaemia	109/146 (74.7%)		120/141 (85.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/146 (6.8%)		13/141 (9.2%)
Back pain	10/146 (6.8%)		12/141 (8.5%)
Pain in extremity	7/146 (4.8%)		15/141 (10.6%)
Tendonitis	4/146 (2.7%)		8/141 (5.7%)
Nervous system disorders
Dizziness	11/146 (7.5%)		10/141 (7.1%)
Headache	14/146 (9.6%)		14/141 (9.9%)
Neuropathy peripheral	2/146 (1.4%)		7/141 (5%)
Tremor	8/146 (5.5%)		17/141 (12.1%)
Psychiatric disorders
Depression	11/146 (7.5%)		6/141 (4.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	53/146 (36.3%)		63/141 (44.7%)
Cough	29/146 (19.9%)		11/141 (7.8%)
Dyspnoea	9/146 (6.2%)		2/141 (1.4%)
Oropharyngeal pain	14/146 (9.6%)		2/141 (1.4%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	6/146 (4.1%)		13/141 (9.2%)

Limitations/Caveats

Data for some secondary endpoints were not tabulated or analyzed for this study and some concomitant medication data were not accurately recorded and tabulated due to lack of resources resulting from scaling down of Exubera® development.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.