Efficacy and Safety of Inhaled Insulin Compared With Subcutaneous Human Insulin Therapy in Adults With Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT00136916
• Recruitment Status: Terminated
• First Posted: August 29, 2005
• Results First Posted: January 18, 2010
• Last Update Posted: February 18, 2010
• Sponsor: Pfizer
• Information provided by: Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diabetes Mellitus
• Interventions: Drug: Inhaled Insulin; Drug: Subcutaneous insulin
• Enrollment: 635

Participant Flow

Recruitment Details
Pre-assignment Details	At screening visit and during the 4-week run-in phase subjects received subcutaneous insulin regime of 2 to 3 daily doses (QD) of regular insulin-/short-acting insulin analog (lispro or aspart) and 1 or 2 doses QD of intermediate or long-acting insulin (neutral protamine hagedorn [NPH] insulin or Ultralente®) or insulin glargine QD at bedtime.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Period Title: Overall Study
Started	319	316
Received Treatment	316	311
Completed	194 [1]	212 [1]
Not Completed	125	104
Reason Not Completed
Never received study treatment	3	5
Death	1	3
Adverse Event	27	8
Laboratory abnormality	0	1
Lack of Efficacy	13	3
Lost to Follow-up	12	14
Withdrawal by Subject	44	46
Other	22	24
Discontinued in follow up period	3	0
[1] At study termination, active subjects completed end-of-study assessment and 3-month follow-up visit

Baseline Characteristics

Arm/Group Title		Inhaled Insulin (Exubera®)	Subcutaneous Insulin	Total
Arm/Group Description		Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.	Total of all reporting groups
Overall Number of Baseline Participants		316	311	627
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	316 participants	311 participants	627 participants
Between 26 and 35 years		2	7	9
Between 36 and 45 years		36	49	85
Between 46 and 55 years		100	93	193
Between 56 and 65 years		117	101	218
Between 66 and 75 years		61	61	122
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	316 participants	311 participants	627 participants
		56.7 (9.2)	55.5 (9.9)	56.1 (9.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	316 participants	311 participants	627 participants
	Female	111 35.1%	118 37.9%	229 36.5%
	Male	205 64.9%	193 62.1%	398 63.5%

Outcome Measures

1. Primary Outcome

Title	Change From Month 3 in Forced Expiratory Volume in 1 Second (FEV1)
Description	Change from Month 3: mean of (value of observed FEV1 [forced expiratory volume in the first second of forced exhalation] in liters [L] at treatment observation minus Month 3 value).
Time Frame	Month 3 through extension Month 60

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) FEV1: received at least 1 dose treatment, had baseline and at least 1 post-baseline FEV1. Due to study termination, originally planned inferential analysis for change from Month 3 through extension Month 60 was not done. Cross reference outcome measure: change from baseline in FEV1.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

2. Primary Outcome

Title	Change From Baseline in FEV1
Description	Change from baseline: mean of (value of observed FEV1 [L] at treatment observation minus baseline value).
Time Frame	Baseline through extension follow up Month 3

Outcome Measure Data

Analysis Population Description

FAS FEV1; extension Month 36 (M36) Last Observation Carried Forward (LOCF) based on data in the extension phase only; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively. Cross reference outcome measure: change from Month 3 in forced expiratory volume in 1 second.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	311	304
Mean (Standard Deviation); Unit of Measure: L
Baseline (n=311, 304)	2.91 (0.68)	2.93 (0.71)
Month 3 (M3) (n=290, 291)	-0.06 (0.13)	-0.01 (0.15)
M6 (n=281, 280)	-0.05 (0.16)	-0.05 (0.17)
M9 (n=266, 276)	-0.08 (0.17)	-0.07 (0.16)
M12 (n=259, 263)	-0.09 (0.17)	-0.07 (0.16)
M15 (n=247, 250)	-0.12 (0.18)	-0.09 (0.17)
M18 (n=237, 236)	-0.12 (0.18)	-0.10 (0.18)
M21 (n=232, 233)	-0.13 (0.18)	-0.11 (0.18)
M24 (n=223, 226)	-0.15 (0.19)	-0.13 (0.18)
Follow-up (FU) M1 (n=249, 221)	-0.14 (0.18)	-0.14 (0.19)
FU M3 (n=248, 231)	-0.13 (0.21)	-0.14 (0.20)
FU M6 (n=242, 220)	-0.12 (0.20)	-0.15 (0.18)
Extension (Ext) M1 (n=161, 163)	-0.16 (0.20)	-0.16 (0.20)
Ext M3 (n=157, 158)	-0.19 (0.21)	-0.16 (0.19)
Ext M6 (n=148, 159)	-0.20 (0.21)	-0.17 (0.20)
Ext M9 (n=144, 157)	-0.19 (0.21)	-0.16 (0.21)
Ext M12 (n=144, 157)	-0.20 (0.21)	-0.18 (0.22)
Ext M15 (n=141, 145)	-0.22 (0.23)	-0.21 (0.20)
Ext M18 (n=135, 139)	-0.22 (0.23)	-0.21 (0.22)
Ext M21 (n=132, 143)	-0.23 (0.24)	-0.21 (0.21)
Ext M24 (n=125, 131)	-0.24 (0.24)	-0.23 (0.22)
Ext M27 (n=124, 125)	-0.25 (0.23)	-0.24 (0.22)
Ext M30 (n=125, 126)	-0.24 (0.22)	-0.23 (0.23)
Ext M33 (n=98, 113)	-0.24 (0.24)	-0.24 (0.22)
Ext M36 (n=54, 60)	-0.25 (0.18)	-0.28 (0.17)
Ext M36 [LOCF] (n=171, 169)	-0.24 (0.24)	-0.24 (0.21)
Ext FU M3 (n=119, 115)	-0.24 (0.21)	-0.25 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.045
	Confidence Interval	90%; -0.064 to -0.026
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.011
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.003
	Confidence Interval	90%; -0.025 to 0.020
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.014
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M9
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.010
	Confidence Interval	90%; -0.033 to 0.013
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.014
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.020
	Confidence Interval	90%; -0.044 to 0.004
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.014
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M15
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.023
	Confidence Interval	90%; -0.048 to 0.003
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.015
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M18
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.023
	Confidence Interval	90%; -0.050 to 0.004
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.016
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M21
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.020
	Confidence Interval	90%; -0.047 to 0.007
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.017
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.026
	Confidence Interval	90%; -0.054 to 0.002
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.017
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M1
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.007
	Confidence Interval	90%; -0.021 to 0.034
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.017
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.014
	Confidence Interval	90%; -0.016 to 0.044
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.018
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.027
	Confidence Interval	90%; -0.002 to 0.055
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.017
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M1
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.004
	Confidence Interval	90%; -0.040 to 0.032
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.022
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.033
	Confidence Interval	90%; -0.070 to 0.004
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.023
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.039
	Confidence Interval	90%; -0.077 to -0.002
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.023
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M9
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.036
	Confidence Interval	90%; -0.075 to 0.003
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.024
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.018
	Confidence Interval	90%; -0.058 to 0.022
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.024
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M15
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.007
	Confidence Interval	90%; -0.034 to 0.048
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.025
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M18
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.011
	Confidence Interval	90%; -0.055 to 0.033
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.027
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M21
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.015
	Confidence Interval	90%; -0.058 to 0.029
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.026
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.015
	Confidence Interval	90%; -0.061 to 0.030
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.028
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M27
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.000
	Confidence Interval	90%; -0.044 to 0.043
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.026
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M30
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.005
	Confidence Interval	90%; -0.051 to 0.040
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.027
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M33
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.008
	Confidence Interval	90%; -0.042 to 0.058
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.030
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline pulmonary function tests (PFTs), center, age, sex, and height.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M36
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.024
	Confidence Interval	90%; -0.030 to 0.077
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.032
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M36 LOCF
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.003
	Confidence Interval	90%; -0.042 to 0.035
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.023
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height. Ext M36 (LOCF) based on data in the extension phase only.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.019
	Confidence Interval	90%; -0.023 to 0.062
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.026
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

3. Primary Outcome

Title	Annual Rate of Change in FEV1
Description	Annual rate of change in FEV1 calculated as slope over time [visit] for forced expiratory volume in 1 second measured as liters per year (L/yr).
Time Frame	Week -2 through extension follow up Month 3 or end of study

Outcome Measure Data

Analysis Population Description

FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of Annual rate of change in FEV1 were not summarized as planned.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

4. Primary Outcome

Title	Summary of ≥ 15 % Decliners in FEV1
Description	Number of subjects with a post-baseline FEV1 decrease of ≥ 15 % [(baseline observed value - visit observed value)/(baseline observed value) * 100]; in the absence of an obvious intercurrrent illness, a repeat FEV1 was performed.
Time Frame	Month 3 through extension follow up Month 3

Outcome Measure Data

Analysis Population Description

FAS FEV1; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	311	304
Measure Type: Number; Unit of Measure: participants
M3 (n=290, 291)	2	2
M6 (n=281, 280)	3	4
M9 (n=266, 276)	7	5
M12 (n=259, 263)	7	4
M15 (n=247, 250)	13	6
M18 (n=237, 236)	10	8
M21 (n=232, 233)	12	8
M24 (n=223, 226)	14	13
FU M1 (n=249, 221)	11	7
FU M3 (n=248, 231)	16	15
FU M6 (n=242, 220)	13	11
Ext M1 (n=161, 163)	12	6
Ext M3 (n=157, 158)	12	5
Ext M6 (n=148, 159)	14	8
Ext M9 (n=144, 157)	11	10
Ext M12 (n=144, 157)	19	13
Ext M15 (n=141, 145)	15	11
Ext M18 (n=135, 139)	17	18
Ext M21 (n=132, 143)	22	11
Ext M24 (n=125, 131)	22	16
Ext M27 (n=124, 125)	18	14
Ext M30 (n=125, 126)	20	18
Ext M33 (n=98, 113)	10	12
Ext M36 (n=54, 60)	5	6
Ext FU M3 (n=119, 115)	14	19

5. Primary Outcome

Title	Annual Rate of Change in Carbon Monoxide Diffusion Capacity (DLco)
Description	Annual rate of change in DLco calculated as slope over time (visit) measured as milliliters per minute per millimeters of mercury per year (ml/min/mmHg/yr).
Time Frame	Week -2 through extension follow up Month 3 or end of study

Outcome Measure Data

Analysis Population Description

FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of Annual rate of change in DLco were not summarized as planned. Cross reference outcome measure: change from baseline in Carbon Monoxide Diffusion Capacity (DLco).

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

6. Primary Outcome

Title	Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco)
Description	Change from baseline: mean of (value of observed DLco [milliliters per minute per millimeters of mercury (ml/min/mmHg)] at treatment observation minus baseline value).
Time Frame	Baseline through extension follow up Month 3

Outcome Measure Data

Analysis Population Description

FAS FEV1; extension M36 LOCF based on data in the extension phase only; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively. Cross reference outcome measure Annual rate of change in Carbon Monoxide Diffusion Capacity (DLco).

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	308	303
Mean (Standard Deviation); Unit of Measure: ml/min/mmHg
Baseline (n=308, 303)	24.13 (5.54)	23.97 (5.72)
M3 (n=289, 290)	-0.57 (1.60)	-0.32 (1.62)
M6 (n=278, 280)	-0.56 (1.62)	-0.44 (1.73)
M9 (n=266, 272)	-0.67 (1.78)	-0.72 (1.77)
M12 (n=258, 263)	-0.72 (1.86)	-0.41 (1.87)
M15 (n=246, 248)	-0.81 (1.83)	-0.56 (1.96)
M18 (n=237, 232)	-0.86 (1.95)	-0.65 (1.92)
M21 (n=231, 231)	-0.89 (1.98)	-0.67 (1.92)
M24 (n=221, 223)	-0.74 (2.10)	-0.81 (2.06)
FU M1 (n=247, 220)	-0.46 (2.05)	-1.02 (2.01)
FU M3 (n=247, 231)	-0.58 (2.07)	-0.90 (2.15)
FU M6 (n=241, 219)	-0.64 (2.15)	-0.95 (2.11)
Ext M1 (n=159, 161)	-1.01 (2.08)	-1.09 (2.15)
Ext M3 (n=157, 157)	-1.07 (2.10)	-1.16 (2.45)
Ext M6 (n=148, 157)	-1.48 (1.87)	-1.26 (2.38)
Ext M9 (n=143, 155)	-1.15 (2.31)	-1.36 (2.54)
Ext M12 (n=141, 155)	-1.49 (2.22)	-1.59 (2.38)
Ext M15 (n=141, 142)	-1.49 (2.25)	-1.46 (2.41)
Ext M18 (n=132, 138)	-1.54 (2.25)	-1.63 (2.21)
Ext M21 (n=129, 142)	-1.33 (2.45)	-1.64 (2.45)
Ext M24 (n=124, 130)	-1.39 (2.27)	-1.46 (2.43)
Ext M27 (n=123, 124)	-1.35 (2.48)	-1.44 (2.41)
Ext M30 (n=124, 125)	-1.75 (2.13)	-1.62 (2.55)
Ext M33 (n=98, 113)	-1.47 (2.05)	-1.61 (2.25)
Ext M36 (n=52, 60)	-1.22 (2.16)	-1.87 (2.23)
Ext M36 [LOCF] (n=171, 169)	-1.39 (2.31)	-1.77 (2.46)
Ext FU M3 (n=118, 114)	-1.12 (2.15)	-1.69 (2.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.251
	Confidence Interval	90%; -0.466 to -0.037
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.130
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.095
	Confidence Interval	90%; -0.323 to 0.134
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.139
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M9
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.084
	Confidence Interval	90%; -0.158 to 0.325
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.146
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.266
	Confidence Interval	90%; -0.524 to -0.009
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.156
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M15
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.181
	Confidence Interval	90%; -0.453 to 0.091
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.165
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M18
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.141
	Confidence Interval	90%; -0.427 to 0.145
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.173
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M21
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.155
	Confidence Interval	90%; -0.445 to 0.134
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.176
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.119
	Confidence Interval	90%; -0.193 to 0.431
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.189
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M1
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.617
	Confidence Interval	90%; 0.322 to 0.911
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.179
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.354
	Confidence Interval	90%; 0.051 to 0.657
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.184
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.318
	Confidence Interval	90%; 0.011 to 0.626
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.186
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M1
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.136
	Confidence Interval	90%; -0.227 to 0.500
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.220
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.098
	Confidence Interval	90%; -0.289 to 0.485
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.235
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.202
	Confidence Interval	90%; -0.576 to 0.172
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.226
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M9
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.245
	Confidence Interval	90%; -0.180 to 0.669
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.257
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.126
	Confidence Interval	90%; -0.284 to 0.535
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.248
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M15
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.023
	Confidence Interval	90%; -0.395 to 0.441
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.253
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M18
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.146
	Confidence Interval	90%; -0.262 to 0.554
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.247
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M21
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.321
	Confidence Interval	90%; -0.138 to 0.780
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.278
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.043
	Confidence Interval	90%; -0.419 to 0.506
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.280
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M27
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.190
	Confidence Interval	90%; -0.279 to 0.659
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.284
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M30
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.117
	Confidence Interval	90%; -0.579 to 0.346
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.280
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M33
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.262
	Confidence Interval	90%; -0.189 to 0.714
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.273
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M36
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.267
	Confidence Interval	90%; -0.370 to 0.904
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.383
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M36 LOCF
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.399
	Confidence Interval	90%; -0.003 to 0.802
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.244
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height. Ext M36 (LOCF) based on data in the extension phase only.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.619
	Confidence Interval	90%; 0.137 to 1.102
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.292
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline PFTs, center, age, sex, and height.

7. Primary Outcome

Title	Summary of ≥ 20 % Decliners in DLco
Description	Number of subjects with a post-baseline DLco decrease of ≥ 20 % [(baseline observed value - visit observed value)/(baseline observed value) * 100]; in the absence of an obvious intercurrrent illness, a repeat DLco was performed.
Time Frame	Month 3 through extension follow up Month 3

Outcome Measure Data

Analysis Population Description

FAS FEV1; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	308	303
Measure Type: Number; Unit of Measure: participants
M3 (n=289, 290)	0	2
M6 (n=278, 280)	1	2
M9 (n=266, 272)	0	3
M12 (n=258, 263)	4	3
M15 (n=246, 248)	1	2
M18(n=237, 232)	2	5
M21 (n=231, 231)	0	3
M24 (n=221, 223)	4	5
FU M1 (n=247, 220)	2	4
FU M3 (n=247, 231)	3	6
FU M6 (n=241, 219)	5	5
Ext M1 (n=159, 161)	3	3
Ext M3 (n=157, 157)	3	8
Ext M6 (n=148, 157)	4	6
Ext M9 (n=143, 155)	4	7
Ext M12 (n=141, 155)	8	9
Ext M15(n=141, 142)	4	6
Ext M18 (n=132, 138)	6	7
Ext M21(n=129, 142)	4	8
Ext M24 (n=124, 130)	5	7
Ext M27(n=123, 124)	7	8
Ext M30 (n=124, 125)	7	11
Ext M33(n=98, 113)	1	4
Ext M36 (n=52, 60)	2	3
Ext FU M3 (n=118, 114)	6	10

8. Secondary Outcome

Title	Forced Vital Capacity (FVC)
Description	Forced Vital Capacity (FVC) measured in liters (L).
Time Frame	Week -3 through extension follow up Month 3 or end of study

Outcome Measure Data

Analysis Population Description

FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of FVC were not summarized as planned.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

9. Secondary Outcome

Title	Total Lung Capacity (TLC)
Description	Total Lung Capacity measured in liters (L).
Time Frame	Baseline through extension follow up Month 3

Outcome Measure Data

Analysis Population Description

FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of TLC were not summarized as planned.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

10. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Description	Change from baseline: mean of (value of observed HbA1c [%] at treatment observation minus baseline value).
Time Frame	Baseline through extension follow up Month 3

Outcome Measure Data

Analysis Population Description

FAS HbA1c: received at least 1 dose of study treatment, had baseline HbA1c and at least 1 post-baseline HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	315	303
Mean (Standard Deviation); Unit of Measure: percent
Baseline (n=315, 303)	7.66 (1.12)	7.77 (1.12)
Week 6 (W6) (n=291, 280)	-0.64 (0.67)	-0.60 (0.70)
M3 (n=296, 291)	-0.80 (0.86)	-0.73 (0.89)
M6 (n=284, 287)	-0.67 (0.94)	-0.68 (1.00)
M9 (n=270, 280)	-0.56 (0.98)	-0.61 (0.93)
M12 (n=261, 263)	-0.45 (0.94)	-0.58 (1.00)
M15(n=252, 258)	-0.43 (1.00)	-0.51 (1.00)
M18(n=244, 241)	-0.42 (1.02)	-0.53 (1.06)
M21 (n=236, 238)	-0.43 (1.04)	-0.52 (1.02)
M24 (n=226, 234)	-0.35 (1.09)	-0.48 (1.13)
FU M3 (n=225, 226)	-0.41 (1.04)	-0.44 (1.06)
FU M6 (n=230, 230)	-0.27 (1.12)	-0.31 (1.06)
Ext M1 (n=167, 162)	-0.41 (1.16)	-0.40 (1.05)
Ext M3 (n=164, 162)	-0.33 (1.19)	-0.42 (1.05)
Ext M6 (n=157, 163)	-0.26 (1.11)	-0.40 (1.10)
Ext M9 (n=152, 157)	-0.11 (1.15)	-0.26 (1.13)
Ext M12 (n=150, 157)	-0.08 (1.19)	-0.17 (1.16)
Ext M15(n=146, 151)	-0.17 (1.30)	-0.25 (1.15)
Ext M18 (n=145, 145)	-0.20 (1.19)	-0.29 (1.17)
Ext M21(n=137, 147)	-0.13 (1.16)	-0.20 (1.20)
Ext M24 (n=131, 137)	-0.18 (1.21)	-0.23 (1.11)
Ext M27(n=129, 132)	-0.18 (1.13)	-0.28 (1.20)
Ext M30 (n=129, 129)	-0.20 (1.19)	-0.30 (1.19)
Ext M33(n=104, 116)	8.54 (88.44)	-0.18 (1.17)
Ext M36 (n=55, 64)	-0.20 (1.15)	-0.30 (1.18)
Ext FU M3 (n=117, 116)	-0.11 (1.40)	-0.17 (1.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.119
	Confidence Interval	90%; -0.215 to -0.023
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.058
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.023
	Confidence Interval	90%; -0.133 to 0.087
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.067
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M9
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.010
	Confidence Interval	90%; -0.104 to 0.124
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.069
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.091
	Confidence Interval	90%; -0.033 to 0.214
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.075
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M15
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.052
	Confidence Interval	90%; -0.081 to 0.185
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.081
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M18
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.090
	Confidence Interval	90%; -0.054 to 0.234
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.087
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M21
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.068
	Confidence Interval	90%; -0.073 to 0.208
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.085
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.100
	Confidence Interval	90%; -0.058 to 0.257
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.096
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.006
	Confidence Interval	90%; -0.143 to 0.154
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.090
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.036
	Confidence Interval	90%; -0.119 to 0.190
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.094
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M1
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.019
	Confidence Interval	90%; -0.200 to 0.161
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.110
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.081
	Confidence Interval	90%; -0.101 to 0.263
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.110
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.141
	Confidence Interval	90%; -0.038 to 0.320
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.108
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M9
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.150
	Confidence Interval	90%; -0.041 to 0.342
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.116
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.104
	Confidence Interval	90%; -0.090 to 0.298
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.118
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M15
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.074
	Confidence Interval	90%; -0.132 to 0.279
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.125
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M18
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.087
	Confidence Interval	90%; -0.111 to 0.284
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.120
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M21
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.064
	Confidence Interval	90%; -0.141 to 0.270
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.124
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.047
	Confidence Interval	90%; -0.156 to 0.249
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.123
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M27
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.067
	Confidence Interval	90%; -0.138 to 0.272
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.124
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M30
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.046
	Confidence Interval	90%; -0.171 to 0.264
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.132
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M33
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.824
	Confidence Interval	90%; -3.920 to 23.569
	Parameter Dispersion	Type: Standard Error of the mean; Value: 8.319
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M36
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.011
	Confidence Interval	90%; -0.316 to 0.337
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.197
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.024
	Confidence Interval	90%; -0.245 to 0.292
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.163
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline HbA1c, and center.

11. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG)
Description	Change from baseline: mean of (value of observed FPG [milligrams per deciliter (mg/dL)] at treatment observation minus baseline value).
Time Frame	Baseline through extension follow up Month 3

Outcome Measure Data

Analysis Population Description

FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	315	303
Mean (Standard Deviation); Unit of Measure: mg/dL
Baseline (n=315, 303)	158.13 (42.71)	154.53 (41.51)
W6 (n=282, 276)	-23.36 (51.69)	-12.55 (50.46)
M3 (n=294, 290)	-26.38 (52.72)	-12.77 (54.93)
M6 (n=281, 285)	-25.21 (53.48)	-9.05 (68.42)
M9 (n=267, 279)	-26.68 (54.95)	-10.41 (56.42)
M12 (n=260, 263)	-20.55 (59.68)	-7.60 (60.03)
M15(n=253, 255)	-21.37 (54.53)	-8.82 (55.57)
M18(n=242, 238)	-24.52 (54.50)	-7.69 (58.47)
M21(n=232, 237)	-25.95 (53.06)	-13.14 (54.66)
M24 (n=226, 232)	-24.02 (54.45)	-8.91 (65.24)
FU M3 (n=5, 4)	-22.60 (44.65)	-4.08 (32.08)
FU M6 (n=161, 156)	-2.85 (66.18)	-1.56 (71.72)
Ext M1 (n=165, 162)	-17.91 (60.96)	-7.34 (60.98)
Ext M3 (n=162, 159)	-18.16 (66.59)	-9.29 (62.50)
Ext M6 (n=152, 161)	-15.65 (67.18)	-4.34 (61.96)
Ext M9 (n=149, 155)	-13.99 (61.68)	-6.06 (60.86)
Ext M12 (n=148, 155)	-12.53 (72.25)	-4.98 (62.92)
Ext M15(n=143, 143)	-6.88 (68.85)	-4.23 (65.21)
Ext M18 (n=136, 138)	-17.23 (65.97)	-10.32 (63.11)
Ext M21(n=132, 144)	-12.86 (63.98)	-6.53 (64.09)
Ext M24 (n=129, 136)	-14.45 (61.65)	-3.47 (68.57)
Ext M27 (n=128, 129)	-21.68 (58.35)	-3.76 (63.31)
Ext M30 (n=127, 130)	-11.80 (62.82)	-6.40 (61.47)
Ext M33(n=103, 115)	-16.26 (63.44)	-7.35 (66.21)
Ext M36 (n=55, 64)	-28.61 (65.99)	-13.35 (53.97)
Ext FU M3 (n=115, 118)	-2.87 (81.19)	1.88 (64.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.39
	Confidence Interval	90%; -19.07 to -5.710
	Parameter Dispersion	Type: Standard Error of the mean; Value: 4.054
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-14.21
	Confidence Interval	90%; -22.11 to -6.312
	Parameter Dispersion	Type: Standard Error of the mean; Value: 4.795
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.96
	Confidence Interval	90%; -19.07 to -2.852
	Parameter Dispersion	Type: Standard Error of the mean; Value: 4.920
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.56
	Confidence Interval	90%; -20.89 to -4.232
	Parameter Dispersion	Type: Standard Error of the mean; Value: 5.052
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.83
	Confidence Interval	90%; -80.69 to 47.019
	Parameter Dispersion	Type: Standard Error of the mean; Value: 21.867
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.578
	Confidence Interval	90%; -9.257 to 14.412
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.173
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M1
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.460
	Confidence Interval	90%; -19.37 to 0.450
	Parameter Dispersion	Type: Standard Error of the mean; Value: 6.007
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.481
	Confidence Interval	90%; -20.11 to 1.153
	Parameter Dispersion	Type: Standard Error of the mean; Value: 6.446
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.76
	Confidence Interval	90%; -21.95 to 0.438
	Parameter Dispersion	Type: Standard Error of the mean; Value: 6.785
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M9
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.827
	Confidence Interval	90%; -16.98 to 3.328
	Parameter Dispersion	Type: Standard Error of the mean; Value: 6.154
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.287
	Confidence Interval	90%; -19.15 to 4.579
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.192
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M15
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.848
	Confidence Interval	90%; -13.76 to 10.066
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.219
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M18
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.022
	Confidence Interval	90%; -20.83 to 2.790
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.156
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M21
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.078
	Confidence Interval	90%; -18.99 to 4.834
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.217
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.53
	Confidence Interval	90%; -24.63 to -0.429
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.329
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M27
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-19.07
	Confidence Interval	90%; -30.45 to -7.685
	Parameter Dispersion	Type: Standard Error of the mean; Value: 6.895
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M30
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.220
	Confidence Interval	90%; -15.15 to 8.705
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.223
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M33
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.490
	Confidence Interval	90%; -21.09 to 4.107
	Parameter Dispersion	Type: Standard Error of the mean; Value: 7.625
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M36
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-21.88
	Confidence Interval	90%; -36.66 to -7.105
	Parameter Dispersion	Type: Standard Error of the mean; Value: 8.906
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.673
	Confidence Interval	90%; -19.16 to 9.812
	Parameter Dispersion	Type: Standard Error of the mean; Value: 8.770
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline fasting plasma glucose, and center.

12. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	Change from baseline: mean of (value of observed body weight [kilograms (kg)] at treatment observation minus baseline value).
Time Frame	Baseline through extension follow up Month 3

Outcome Measure Data

Analysis Population Description

FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	314	302
Mean (Standard Deviation); Unit of Measure: kg
Baseline (n=314, 302)	87.18 (14.75)	88.31 (15.50)
W4 (n=280, 270)	0.63 (2.11)	0.83 (1.86)
W8 (n=289, 281)	1.07 (2.41)	1.00 (2.31)
M3 (n=288, 290)	1.08 (2.75)	1.13 (2.55)
W18(n=280, 285)	1.33 (3.13)	1.76 (3.03)
M6 (n=276, 277)	1.15 (3.59)	1.89 (3.53)
M9 (n=269, 274)	1.50 (3.95)	2.15 (3.90)
M12 (n=259, 264)	1.75 (4.29)	2.37 (4.34)
M15(n=247, 249)	1.88 (4.33)	2.62 (4.49)
M18(n=237, 235)	1.79 (4.53)	2.93 (4.85)
M21(n=232, 232)	1.99 (4.56)	3.04 (5.04)
M24 (n=223, 226)	2.04 (4.86)	3.36 (5.16)
FU M3 (n=249, 231)	2.32 (5.25)	3.63 (5.34)
FU M6 (n=243, 218)	2.38 (5.34)	4.09 (7.70)
Ext M1 (n=161, 162)	2.87 (5.48)	3.75 (5.58)
Ext M3 (n=157, 157)	2.83 (4.78)	4.14 (5.69)
Ext M6 (n=148, 159)	3.15 (5.70)	4.01 (6.07)
Ext M9 (n=144, 156)	2.95 (5.95)	3.89 (5.87)
Ext M12 (n=144, 156)	2.96 (6.00)	4.19 (6.12)
Ext M15 (n=142, 145)	3.12 (5.91)	4.54 (6.26)
Ext M18 (n=135, 139)	3.33 (9.20)	4.46 (6.12)
Ext M21(n=132, 143)	2.79 (6.90)	5.01 (8.37)
Ext M24 (n=126, 131)	2.94 (6.98)	4.57 (6.37)
Ext M27(n=125, 125)	2.99 (6.94)	5.58 (9.62)
Ext M30 (n=125, 126)	3.39 (6.43)	4.78 (6.96)
Ext M33(n=99, 113)	2.77 (6.33)	5.22 (7.21)
Ext M36 (n=54, 60)	2.48 (6.61)	5.28 (7.09)
Ext FU M3 (n=119, 115)	2.74 (6.90)	4.44 (6.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.059
	Confidence Interval	90%; -0.416 to 0.299
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.217
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.735
	Confidence Interval	90%; -1.224 to -0.246
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.297
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.642
	Confidence Interval	90%; -1.251 to -0.032
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.370
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.355
	Confidence Interval	90%; -2.120 to -0.589
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.464
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.303
	Confidence Interval	90%; -2.086 to -0.520
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.475
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	FU M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.557
	Confidence Interval	90%; -2.539 to -0.575
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.596
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M1
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.904
	Confidence Interval	90%; -1.898 to 0.090
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.603
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.280
	Confidence Interval	90%; -2.225 to -0.334
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.573
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.834
	Confidence Interval	90%; -1.909 to 0.241
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.652
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M9
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.001
	Confidence Interval	90%; -2.080 to 0.078
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.654
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.316
	Confidence Interval	90%; -2.431 to -0.200
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.676
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M15
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.512
	Confidence Interval	90%; -2.661 to -0.363
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.696
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M18
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.313
	Confidence Interval	90%; -2.824 to 0.198
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.916
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M21
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.399
	Confidence Interval	90%; -3.891 to -0.907
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.904
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.566
	Confidence Interval	90%; -2.867 to -0.265
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.788
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M27
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.720
	Confidence Interval	90%; -4.439 to -1.001
	Parameter Dispersion	Type: Standard Error of the mean; Value: 1.041
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M30
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.401
	Confidence Interval	90%; -2.755 to -0.047
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.820
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M33
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.281
	Confidence Interval	90%; -3.781 to -0.782
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.908
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext M36
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.766
	Confidence Interval	90%; -4.932 to -0.599
	Parameter Dispersion	Type: Standard Error of the mean; Value: 1.305
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Inhaled Insulin (Exubera®), Subcutaneous Insulin
	Comments	Ext FU M3
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.637
	Confidence Interval	90%; -3.120 to -0.153
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.898
	Estimation Comments	Adjusted Primary Analysis Model includes terms of treatment, baseline weight, and center.

13. 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 (units) insulin for inhaled insulin and subcutaneous treatment groups included NPH insulin, Ultralente®, and insulin glargine.
Time Frame	Month 3 through extension Month 36

Outcome Measure Data

Analysis Population Description

FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	315	303
Mean (Standard Deviation); Unit of Measure: units
M3 (n=301, 298)	44.10 (25.60)	47.98 (25.06)
M6 (n=289, 291)	44.03 (26.27)	47.31 (25.47)
M9 (n=275, 284)	43.64 (26.17)	48.11 (26.02)
M12 (n=266, 270)	44.62 (27.43)	48.01 (26.02)
M15 (n=258, 260)	45.02 (27.76)	48.37 (26.48)
M18 (n=243, 242)	46.07 (27.77)	48.93 (27.60)
M21 (n=240, 240)	46.67 (29.06)	49.84 (28.73)
M24 (n=229, 237)	46.62 (28.55)	50.34 (29.31)
Ext M1 (n=167, 164)	45.29 (28.00)	51.29 (28.45)
Ext M3 (n=165, 162)	45.76 (28.61)	51.62 (28.71)
Ext M6 (n=159, 164)	45.89 (28.61)	52.18 (28.85)
Ext M9 (n=156, 158)	46.51 (29.34)	52.32 (28.89)
Ext M12 (n=151, 158)	46.52 (29.84)	51.72 (29.06)
Ext M15 (n=148, 149)	46.39 (30.12)	52.92 (29.83)
Ext M18 (n=145, 145)	46.31 (31.17)	52.37 (29.78)
Ext M21 (n=137, 148)	46.49 (31.17)	52.68 (29.40)
Ext M24 (n=131, 137)	47.21 (32.42)	52.18 (30.33)
Ext M27 (n=132, 133)	48.13 (32.76)	52.42 (29.87)
Ext M30 (n=131, 130)	48.13 (33.41)	53.22 (29.85)
Ext M33 (n=104, 116)	48.38 (32.47)	51.93 (30.65)
Ext M36 (n=56, 65)	46.42 (31.91)	53.47 (28.96)

14. Secondary Outcome

Title	Total Daily Long-acting Insulin (Adjusted for Body Weight)
Description	Total daily dose of long-acting insulin adjusted for body weight (units per kilogram [kg]). Long-acting (units) insulin for inhaled insulin and subcutaneous treatment groups included NPH insulin, Ultralente®, and insulin glargine.
Time Frame	Month 3 through extension Month 36

Outcome Measure Data

Analysis Population Description

FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	315	303
Mean (Standard Deviation); Unit of Measure: units/kg
M3 (n=301, 298)	0.51 (0.29)	0.54 (0.27)
M6 (n=289, 291)	0.50 (0.29)	0.54 (0.28)
M9 (n=275, 284)	0.50 (0.29)	0.55 (0.29)
M12 (n=266, 270)	0.51 (0.30)	0.55 (0.29)
M15 (n=258, 260)	0.52 (0.31)	0.56 (0.30)
M18 (n=243, 242)	0.53 (0.31)	0.57 (0.31)
M21 (n=240, 240)	0.53 (0.32)	0.57 (0.32)
M24 (n=229, 237)	0.54 (0.32)	0.58 (0.32)
Ext M1 (n=167, 164)	0.53 (0.33)	0.59 (0.31)
Ext M3 (n=165, 162)	0.53 (0.34)	0.59 (0.31)
Ext M6 (n=159, 164)	0.54 (0.34)	0.60 (0.31)
Ext M9 (n=156, 158)	0.54 (0.35)	0.60 (0.31)
Ext M12 (n=151, 158)	0.54 (0.36)	0.60 (0.32)
Ext M15 (n=148, 149)	0.54 (0.36)	0.61 (0.32)
Ext M18 (n=145, 145)	0.54 (0.37)	0.61 (0.32)
Ext M21 (n=137, 148)	0.54 (0.37)	0.61 (0.32)
Ext M24 (n=131, 137)	0.55 (0.39)	0.61 (0.34)
Ext M27 (n=132, 133)	0.56 (0.39)	0.61 (0.33)
Ext M30 (n=131, 130)	0.56 (0.41)	0.62 (0.33)
Ext M33 (n=104, 116)	0.56 (0.37)	0.61 (0.34)
Ext M36 (n=56, 65)	0.53 (0.37)	0.61 (0.31)

15. Secondary Outcome

Title	Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight)
Description	Total daily dose of short-acting insulin unadjusted for body weight. Short-acting insulin (milligrams [mg]) for the inhaled insulin treatment group was inhaled insulin; short-acting insulin (units) for the subcutaneous insulin treatment group included insulin lispro, insulin aspart, and regular insulin.
Time Frame	Month 3 through extension Month 36

Outcome Measure Data

Analysis Population Description

FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®) (mg)	Subcutaneous Insulin (Units)
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	315	303
Mean (Standard Deviation); Unit of Measure: mg, units
M3 (n=302, 299)	12.66 (6.80)	31.15 (18.75)
M6 (n=290, 292)	13.18 (6.90)	31.73 (19.08)
M9 (n=275, 285)	13.57 (7.57)	31.58 (18.89)
M12 (n=266, 270)	14.40 (7.90)	31.94 (19.29)
M15 (n=258, 261)	14.70 (8.06)	31.88 (19.37)
M18 (n=245, 242)	14.91 (8.41)	32.79 (20.70)
M21 (n=240, 242)	15.09 (8.55)	33.18 (20.92)
M24 (n=229, 238)	15.43 (8.65)	34.04 (21.84)
Ext M1 (n=167, 164)	13.89 (8.47)	34.52 (24.52)
Ext M3 (n=165, 163)	14.62 (9.18)	35.29 (23.19)
Ext M6 (n=159, 165)	14.62 (9.16)	35.43 (24.80)
Ext M9 (n=156, 161)	14.82 (9.10)	35.68 (24.72)
Ext M12 (n=151, 160)	15.42 (9.81)	36.56 (26.34)
Ext M15 (n=148, 151)	15.48 (9.90)	36.27 (25.51)
Ext M18 (n=145, 146)	15.57 (9.93)	37.37 (26.29)
Ext M21 (n=138, 149)	15.94 (10.41)	36.80 (27.09)
Ext M24 (n=131, 138)	15.46 (9.70)	38.51 (29.06)
Ext M27 (n=132, 134)	16.25 (10.30)	38.54 (28.13)
Ext M30 (n=131, 131)	16.56 (10.63)	39.01 (28.66)
Ext M33 (n=105, 117)	16.51 (10.43)	40.33 (30.81)
Ext M36 (n=56, 66)	17.25 (11.30)	42.34 (28.72)

16. Secondary Outcome

Title	Total Daily Short-acting Insulin Dose (Adjusted for Body Weight)
Description	Total daily dose of short-acting insulin adjusted for body weight. Short-acting insulin (mg) for the inhaled insulin treatment group was inhaled insulin (mg divided by kg); short-acting insulin (units) for the subcutaneous insulin treatment group included insulin lispro, insulin aspart, and regular insulin (units divided by kg).
Time Frame	Month 3 through extension Month 36

Outcome Measure Data

Analysis Population Description

FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®) (mg)	Subcutaneous Insulin (Units)
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	315	303
Mean (Standard Deviation); Unit of Measure: mg/kg, units/kg
M3 (n=302, 299)	0.15 (0.07)	0.36 (0.22)
M6 (n=290, 292)	0.15 (0.08)	0.36 (0.22)
M9 (n=275, 285)	0.16 (0.08)	0.36 (0.22)
M12 (n=266, 270)	0.17 (0.09)	0.37 (0.23)
M15 (n=258, 261)	0.17 (0.09)	0.37 (0.24)
M18 (n=245, 242)	0.17 (0.09)	0.38 (0.25)
M21 (n=240, 242)	0.17 (0.09)	0.39 (0.26)
M24 (n=229, 238)	0.18 (0.10)	0.40 (0.27)
Ext M1 (n=167, 164)	0.16 (0.09)	0.40 (0.30)
Ext M3 (n=165, 163)	0.17 (0.10)	0.41 (0.26)
Ext M6 (n=159, 165)	0.17 (0.10)	0.41 (0.30)
Ext M9 (n=156, 161)	0.17 (0.10)	0.42 (0.30)
Ext M12 (n=151, 160)	0.18 (0.11)	0.43 (0.32)
Ext M15 (n=148, 151)	0.18 (0.11)	0.42 (0.31)
Ext M18 (n=145, 146)	0.18 (0.11)	0.44 (0.32)
Ext M21 (n=138, 149)	0.18 (0.11)	0.43 (0.33)
Ext M24 (n=131, 138)	0.18 (0.10)	0.45 (0.35)
Ext M27 (n=132, 134)	0.19 (0.11)	0.45 (0.34)
Ext M30 (n=131, 131)	0.19 (0.12)	0.46 (0.34)
Ext M33 (n=105, 117)	0.19 (0.11)	0.47 (0.36)
Ext M36 (n=56, 66)	0.19 (0.12)	0.48 (0.31)

17. Secondary Outcome

Title	Lipid Panel: Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, and Triglycerides
Description	Lipid values for total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides measured as milligrams per deciliter (mg/dL).
Time Frame	Week -4 through Month 24

Outcome Measure Data

Analysis Population Description

FAS: received at least 1 dose of study treatment. Due to early termination of study a limited set of analyses were undertaken and results of Lipids were not summarized as planned.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

18. Secondary Outcome

Title	Hypoglycemic Event Rates
Description	Hypoglycemic event rate; hypoglycemic event identified by characteristic symptoms of hypoglycemia with no blood glucose (BG) check with prompt resolution with food intake, SC glucagon, or intravenous (IV) glucose; characteristic symptoms with BG of 59 mg/dL (3.2 mmol/L) or less with or without symptoms. Crude event rate = total events divided by subject months (elapsed number of months a subject was in the study at each time interval).
Time Frame	Month 1 through extension Month 36

Outcome Measure Data

Analysis Population Description

FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.

Arm/Group Title	Inhaled Insulin (Exubera®)	Subcutaneous Insulin
Arm/Group Description:	Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime.	Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargin