Exubera vs Lispro in a Lantus-based Regimen for Improved Glycemic Control in Type 2 Diabetes

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00348374
• Collaborator: (none)
• Enrollment: 191
• Locations: 63
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The current trial will examine the efficacy and safety of Exubera administered as a mealtime insulin compared to lispro, when added to an existing regimen of basal insulin glargine + or = Oral Agents (OAs). Dose titrations will be provided which should allow a large proportion of subjects to reach target glycosylated hemoglobin (A1C) levels.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Drug: Insulin Lispro; Drug: Exubera	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 191 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Randomized, Open-Label, Parallel Group, Multicenter Trial Assessing The Efficacy Of Exubera Vs. Lispro Introduced Into A Lantus Based Regimen In Suboptimally Controlled Patients With Type 2 Diabetes Mellitus
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Insulin Lispro Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and oral agents.	Drug: Insulin Lispro; Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and oral agents.
Experimental: Exubera Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and oral agents.	Drug: Exubera; Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and oral agents.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at End of Treatment [Baseline, Week 24 (End of Treatment)]

   Change from Baseline in glycosylated hemoglobin A1c (HbA1c %) at Week 24. Change = mean value at Week 24 minus mean value at Baseline.

Secondary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Each Visit [Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24]

   Change in mean glycosylated hemoglobin A1c (HbA1c %) from Baseline to each visit through Week 24. Change = mean value at observation minus mean value at Baseline.

2. Subjects That Attained Glycosylated Hemoglobin A1c (HbA1c) < 7.0%, < 6.5% and < 6.0% at Week 24 [Week 24]

   Number of subjects acheiving glycemic control: HbA1c target levels of <7.0%, <6.5%, and <6.0% at Week 24.

3. Subjects That Attained Glycosylated Hemoglobin A1c (HbA1c) Target Levels of <7%, < 6.5%, and < 6.0% Without an Episode of Severe Hypoglycemia at Week 24 [Week 24]

   Number of subjects that attained HbA1c target levels of <7%, < 6.5%,and <6.0% at Week 24 without an episode of severe hypoglycemia.

4. Change From Baseline in Fasting and 2-hour Postprandial Glucose as Determined by 8-point Self-monitored Blood Glucose Profiles [Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24]

   Mean change from Baseline in fasting and 2-hour postprandial glucose at each visit in 8-point self-monitored blood glucose (SMBG) profiles: includes values prior to each meal (breakfast, lunch and dinner), 2 hours after each meal, at bedtime, and at 2:00 ante meridiem (a.m.) Change=observation value minus Baseline value.

5. Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 12 [Baseline, Week 12]

   Change from Baseine in fasting and postprandial plasma glucose as determined by standardized meal tolerance tests (MTT). Change = mean value at Week 12 minus mean value at Baseline. Time 0 results are for MTT (time 0) and non MTT (implied time 0) subjects.

6. Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 24 [Baseline, Week 24]

   Change from Baseline in fasting and postprandial plasma glucose as determined by standardized meal tolerance tests (MTT). Change = mean value at Week 24 minus mean value at Baseline. Time 0 results are for MTT (time 0) and non MTT (implied time 0) subjects.

7. Change From Baseline in Fasting and Postprandial Lipids as Determined by Standard Meal Tolerance Tests [Baseline, Week 12, Week 24]

   Change from Baseline in fasting and postprandial lipids at Week 12 and Week 24 as determined by standard meal tolerance tests. Change = value at observation minus value at Baseline. Postprandial = 120 mins after meal.

8. Number of Subjects With Change From Baseline in Fasting and Postprandial Markers of Cardiovascular (CV) Risk as Determined by Standardized Meal Tolerance Tests [Week 12, Week 24]

   Cardiovascular risk markers included serum high-sensitivity C-reactive protein (hs-CRP)[mg/L], leptin (ng/mL), adiponectin (ug/mL), and spot urine microalbumin. Change = observation of mean fasting and postprandial markers of cardiovascular risk at Week 12 and Week 24 minus mean Baseline observation.

9. Change From Baseline Weight at Each Visit [Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24]

   Change = mean body weight at observation minus mean body weight at Baseline.

10. Change From Baseline in Fasting Plasma Lipids [Baseline, Week 12, Week 24]

    Change from baseline in fasting plasma lipids at Week 12 and Week 24. Change = observation mean minus Baseline mean.

11. Change From Baseline in Insulin Glargine Dose at Each Visit (Office and/or Phone) [Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24]

    Change from Baseline in insulin glargine at each visit. Change = mean at observation minus mean Baseline observation. Basal dose = injection of basal insulin (IU) (insulin glargine).

12. Baseline Prandial Insulin Dose (at Each Meal) at Each Visit [Week 0, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24]

    Dose of inhaled insulin prior to each meal at each visit.

13. Number of Subjects With Hypoglycemic Events [Month 1, Month 2, Month 3, Month 4, Month 5, Month 6]

    Severe event = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable/irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or not measured but clinical manifestations reversed by oral carbohydrates or glucose. Non-severe events = events that were mild-moderate.

14. Number of Total Hypoglycemic Events [Month 1, Month 2, Month 3, Month 4, Month 5, Month 6]

    Total number and severity of hypoglycemic events. Severe events = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable or irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or not measured but clinical manifestations reversed by oral carbohydrates or glucose. Non-severe events = events that were mild or moderate.

15. Treatment Exposure for Hypoglycemic Subjects at Each Interval of the Study: Number of Subject Months of Treatment [Month 1, Month 2, Month 3, Month 4, Month 5, Month 6]

    Subject months of treatment = number of days from start of treatment to last day of active treatment + 1 day lag (total number of subjects treated * days treated), including off-drug time)/30.44. Severity: severe = subject unable to treat self, had at least 1 neurological symptom (memory loss, confusion, uncontrollable/irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams/deciliter; or not measured but clinical manifestations were reversed by oral carbohydrates or glucose. Non-severe events = events that were mild or moderate.

16. Crude Hypoglycemic Event Rate [Month 1, Month 2, Month 3, Month 4, Month 5, Month 6]

    Crude event rate = (number of events)/(subject months); severe hypoglycemic events: crude event rate = (number of events)/(100 subject months). Severe = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable or irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or unmeasured but clinical manifestestation reversed by oral carbohydrates or glucose. Non-severe events = mild-moderate.

17. Change From Baseline in Patient Treatment Satisfaction (as Assessed by Patient Satisfaction With Insulin Treatment [PSIT] Questionnaire) [Week 4, Week 24]

    Patient Satisfaction with insulin treatment Questionnaire (PSIT): 15-item self administered questionnaire that measures global satisfaction and two domains (subscales): convenience/ease of use and social comfort in people with type 1 and type 2 diabetes. 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). The scoring of responses to each item is analyzed so that a higher item score indicates more satisfaction. Change = mean Patient Satisfaction of Insulin Treatment (PSIT) score at observation minus mean score at Baseline.

18. Change in Patient Treatment Satisfaction (as Assessed by Patient Satisfaction With Insulin Treatment [PSIT] Questionnaire) From Week 4 to Week 24 [Week 4, Week 24]

    Patient Satisfaction with insulin treatment Questionnaire (PSIT): 15-item self administered questionnaire that measures global satisfaction and two domains (subscales): convenience/ease of use and social comfort in people with type 1 and type 2 diabetes. 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). The scoring of responses to each item is analyzed so that a higher item score indicates more satisfaction. Change = difference in mean Patient Satisfaction with Insulin Treatment (PSIT) score from Week 4 to Week 24.

19. Change From Baseline in 24-hour Mean Glucose Values Measured by Continuous Glucose Monitoring System (CGMS) [Baseline, Week 12, Week 24]

    Mean of 24-hour Continuous Glucose Monitoring (CGMS) glucose values. Change from Baseline = mean at observation minus mean Baseline value.

20. Change From Baseline in Standard Deviation of 24-hour Glucose Values Measured by Continuous Glucose Monitoring System (CGMS) [Baseline, Week 12, Week 24]

    Mean change in standard deviation of all blood glucose values within 24-hour period. Change = mean at observation minus mean at Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults with type 2 diabetes using Lantus® (insulin glargine) as their basal insulin, not at glycemic goal.

Exclusion Criteria:

• lung disease

• current smoking or discontinued smoking within past 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Birmingham	Alabama	United States	35294-307
2	Pfizer Investigational Site	Mobile	Alabama	United States	36608
3	Pfizer Investigational Site	Phoenix	Arizona	United States	85006-2850
4	Pfizer Investigational Site	Malvern	Arkansas	United States	72104
5	Pfizer Investigational Site	Foot Hill Ranch	California	United States	92610
6	Pfizer Investigational Site	Fresno	California	United States	93720
7	Pfizer Investigational Site	Greenbrae	California	United States	94904
8	Pfizer Investigational Site	Los Gatos	California	United States	95032-3739
9	Pfizer Investigational Site	San Diego	California	United States	92120
10	Pfizer Investigational Site	San Mateo	California	United States	94401-3805
11	Pfizer Investigational Site	Tustin	California	United States	92780
12	Pfizer Investigational Site	Denver	Colorado	United States	80209
13	Pfizer Investigational Site	New Britain	Connecticut	United States	06050
14	Pfizer Investigational Site	Washington	District of Columbia	United States	20010-2934
15	Pfizer Investigational Site	Jacksonville	Florida	United States	32205
16	Pfizer Investigational Site	Jacksonville	Florida	United States	32216
17	Pfizer Investigational Site	Miami	Florida	United States	33156
18	Pfizer Investigational Site	West Palm Beach	Florida	United States	33401
19	Pfizer Investigational Site	Winter Park	Florida	United States	32789
20	Pfizer Investigational Site	Columbus	Georgia	United States	31904
21	Pfizer Investigational Site	Decatur	Georgia	United States	30034-1680
22	Pfizer Investigational Site	Honolulu	Hawaii	United States	96813
23	Pfizer Investigational Site	Honululu	Hawaii	United States	96814
24	Pfizer Investigational Site	Idaho Falls	Idaho	United States	83404
25	Pfizer Investigational Site	Chicago	Illinois	United States	60607
26	Pfizer Investigational Site	Gurnee	Illinois	United States	60031
27	Pfizer Investigational Site	Des Moines	Iowa	United States	50314
28	Pfizer Investigational Site	Lexington	Kentucky	United States	40503
29	Pfizer Investigational Site	Louisville	Kentucky	United States	40213
30	Pfizer Investigational Site	Baltimore	Maryland	United States	21234-4607
31	Pfizer Investigational Site	Bethesda	Maryland	United States	20817
32	Pfizer Investigational Site	Boston	Massachusetts	United States	02114
33	Pfizer Investigational Site	Flint	Michigan	United States	48532
34	Pfizer Investigational Site	Minneapolis	Minnesota	United States	55454-1321
35	Pfizer Investigational Site	St. Louis	Missouri	United States	63110
36	Pfizer Investigational Site	St. Louis	Missouri	United States	63141
37	Pfizer Investigational Site	Omaha	Nebraska	United States	68131
38	Pfizer Investigational Site	East Syracuse	New York	United States	13057
39	Pfizer Investigational Site	Greenville	North Carolina	United States	27834
40	Pfizer Investigational Site	Morehead City	North Carolina	United States	28557
41	Pfizer Investigational Site	Statesville	North Carolina	United States	28625
42	Pfizer Investigational Site	Kettering	Ohio	United States	45429
43	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73103
44	Pfizer Investigational Site	Tulsa	Oklahoma	United States	74104
45	Pfizer Investigational Site	Bend	Oregon	United States	97701
46	Pfizer Investigational Site	Bensalem	Pennsylvania	United States	19020
47	Pfizer Investigational Site	Greenville	South Carolina	United States	29615
48	Pfizer Investigational Site	Bartlett	Tennessee	United States	38133
49	Pfizer Investigational Site	Memphis	Tennessee	United States	38119
50	Pfizer Investigational Site	Arlington	Texas	United States	76012
51	Pfizer Investigational Site	Arlington	Texas	United States	76014
52	Pfizer Investigational Site	Dallas	Texas	United States	75230
53	Pfizer Investigational Site	Dallas	Texas	United States	75246
54	Pfizer Investigational Site	El Paso	Texas	United States	79935
55	Pfizer Investigational Site	Houston	Texas	United States	77004
56	Pfizer Investigational Site	San Antonio	Texas	United States	78229
57	Pfizer Investigational Site	Bennington	Vermont	United States	05201-5018
58	Pfizer Investigational Site	Norfolk	Virginia	United States	23502
59	Pfizer Investigational Site	Virginia Beach	Virginia	United States	23462
60	Pfizer Investigational Site	Renton	Washington	United States	98055
61	Pfizer Investigational Site	Spokane	Washington	United States	99208
62	Pfizer Investigational Site	Milwaukee	Wisconsin	United States	53209
63	Pfizer Investigational Site	San Juan		Puerto Rico	00936-5067

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00348374
• Other Study ID Numbers: A2171093
• First Posted: Jul 4, 2006
• Last Update Posted: Mar 16, 2010
• Last Verified: Jul 1, 2009

• Keywords provided by , ,: type two diabetes, insulin, HbA1c
• Additional relevant MeSH terms: Diabetes Mellitus; Insulin Lispro

Study Results

Participant Flow

Recruitment Details	Participants were recruited from 62 centers between June 2006 and August 2008.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Period Title: Overall Study
STARTED	88	103
Received Study Treatment	88	96
COMPLETED	69	71
NOT COMPLETED	19	32

Baseline Characteristics

Arm/Group Title	Exubera®	Insulin Lispro	Total
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).	Total of all reporting groups
Overall Participants	88	96	184
Age, Customized (participants) [Number]
18-44 years	16 18.2%	19 19.8%	35 19%
45-64 years	56 63.6%	51 53.1%	107 58.2%
>=65 years	16 18.2%	26 27.1%	42 22.8%
Sex: Female, Male (Count of Participants)
Female	37 42%	37 38.5%	74 40.2%
Male	51 58%	59 61.5%	110 59.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at End of Treatment
Description	Change from Baseline in glycosylated hemoglobin A1c (HbA1c %) at Week 24. Change = mean value at Week 24 minus mean value at Baseline.
Time Frame	Baseline, Week 24 (End of Treatment)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): subjects who received at least one dose of study medication, had a baseline glycosylated hemoglobin A1c (HbA1c%) measurement, and had a post-baseline HbA1C measurement; last (post-baseline) observation carried forward (LOCF). Number of subjects with HbA1c values at Baseline and Week 24: Exubera® n=81, Lispro n=90.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
Mean (Standard Deviation) [percent]	-1.4 (1.3)	-1.6 (1.0)

2. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Each Visit
Description	Change in mean glycosylated hemoglobin A1c (HbA1c %) from Baseline to each visit through Week 24. Change = mean value at observation minus mean value at Baseline.
Time Frame	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24

Outcome Measure Data

Analysis Population Description

FAS; LOCF; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
Week 4 (n=74, 87)	-0.8 (0.7)	-0.8 (0.6)
Week 8 (n=80, 90)	-1.1 (0.9)	-1.2 (0.9)
Week 12 (n=81, 90)	-1.3 (1.1)	-1.5 (1.0)
Week 16 (n=81, 90)	-1.4 (1.1)	-1.5 (1.1)
Week 20 (n=81, 90)	-1.4 (1.2)	-1.6 (1.1)
Week 24 (n=81, 90)	-1.4 (1.3)	-1.6 (1.0)

3. Secondary Outcome

Title	Subjects That Attained Glycosylated Hemoglobin A1c (HbA1c) < 7.0%, < 6.5% and < 6.0% at Week 24
Description	Number of subjects acheiving glycemic control: HbA1c target levels of <7.0%, <6.5%, and <6.0% at Week 24.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data at Baseline; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
HbA1c < 6.0% (n=61, 64)	8 9.1%	9 9.4%
HbA1c < 6.5% (n=61, 64)	24 27.3%	27 28.1%
HbA1c < 7.0% (n=61, 64)	33 37.5%	41 42.7%

4. Secondary Outcome

Title	Subjects That Attained Glycosylated Hemoglobin A1c (HbA1c) Target Levels of <7%, < 6.5%, and < 6.0% Without an Episode of Severe Hypoglycemia at Week 24
Description	Number of subjects that attained HbA1c target levels of <7%, < 6.5%,and <6.0% at Week 24 without an episode of severe hypoglycemia.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data at Baseline; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
HbA1c < 6.0% (n=61, 63)	8 9.1%	8 8.3%
HbA1c <6.5% (n=61, 63)	24 27.3%	26 27.1%
HbA1c <7% (n=61, 63)	33 37.5%	40 41.7%

5. Secondary Outcome

Title	Change From Baseline in Fasting and 2-hour Postprandial Glucose as Determined by 8-point Self-monitored Blood Glucose Profiles
Description	Mean change from Baseline in fasting and 2-hour postprandial glucose at each visit in 8-point self-monitored blood glucose (SMBG) profiles: includes values prior to each meal (breakfast, lunch and dinner), 2 hours after each meal, at bedtime, and at 2:00 ante meridiem (a.m.) Change=observation value minus Baseline value.
Time Frame	Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
Week 1: Pre-Breakfast [fasting] (n=67, 74)	11.1 (54.1)	9.3 (54.3)
Week 1: 2 Hours Post-Breakfast (n=62, 72)	-36.3 (78.9)	-19.3 (77.5)
Week 1: 2 Hours Post-Lunch (n=62, 73)	-32.2 (76.2)	-27.9 (84.2)
Week 1: 2 Hours Post-Supper (n=61, 68)	-30.7 (74.6)	-32.5 (89.5)
Week 2: Pre-Breakfast [fasting] (n=66, 69)	5.7 (53.5)	5.5 (58.4)
Week 2: 2 Hours Post-Breakfast (n=58, 68)	-43.7 (80.7)	-40.8 (99.3)
Week 2: 2 Hours Post-Lunch (n=59, 69)	-28.1 (73.4)	-52.0 (92.0)
Week 2: 2 Hours Post-Supper (n=62, 67)	-32.6 (80.0)	-54.3 (84.9)
Week 4: Pre-Breakfast [fasting] (n=66, 73)	-2.5 (52.6)	-4.3 (61.9)
Week 4: 2 Hours Post-Breakfast (n=62, 68)	-50.0 (85.0)	-48.5 (87.0)
Week 4: 2 Hours Post-Lunch (n=60, 74)	-45.8 (80.1)	-52.4 (96.0)
Week 4: 2 Hours Post-Supper (n=57, 70)	-44.9 (85.3)	-71.5 (99.0)
Week 8: Pre-Breakfast [fasting] (n=67, 69)	-6.7 (67.0)	-20.8 (48.6)
Week 8: 2 Hours Post-Breakfast (n=61, 69)	-50.2 (89.8)	-59.0 (78.8)
Week 8: 2 Hours Post-Lunch (n=60, 69)	-42.9 (78.5)	-61.0 (95.7)
Week 8: 2 Hours Post-Supper (n=60, 68)	-45.1 (87.8)	-86.5 (98.5)
Week 12: Pre-Breakfast [fasting] (n=57, 73)	-12.2 (63.3)	-22.2 (63.0)
Week 12: 2 Hours Post-Breakfast (n=51, 70)	-46.8 (81.1)	-74.8 (84.3)
Week 12: 2 Hours Post-Lunch (n=49, 71)	-49.1 (87.6)	-60.6 (98.9)
Week 12: 2 Hours Post-Supper (n=52, 69)	-48.2 (84.3)	-81.6 (81.5)
Week 16: Pre-Breakfast [fasting] (n=55, 66)	-26.1 (59.9)	-16.9 (62.0)
Week 16: 2 Hours Post-Breakfast (n=50, 65)	-55.2 (81.3)	-60.5 (81.7)
Week 16: 2 Hours Post-Lunch (n=50, 65)	-56.0 (74.9)	-69.9 (99.2)
Week 16: 2 Hours Post-Supper (n=51, 61)	-53.4 (83.3)	-90.6 (96.1)
Week 20: Pre-Breakfast [fasting] (n=57, 60)	-25.4 (60.7)	-26.3 (59.9)
Week 20: 2 Hours Post-Breakfast (n=51, 59)	-64.2 (67.3)	-78.5 (70.7)
Week 20: 2 Hours Post-Lunch (n=51, 60)	-50.7 (71.1)	-74.1 (91.5)
Week 20: 2 Hours Post-Supper (n=50, 55)	-62.4 (73.4)	-78.7 (83.9)
Week 24: Pre-Breakfast [fasting] (n=56, 55)	-26.6 (64.7)	-27.6 (43.9)
Week 24: 2 Hours Post-Breakfast (n=51, 55)	-61.8 (69.5)	-75.1 (66.3)
Week 24: 2 Hours Post-Lunch (n=50, 56)	-59.6 (69.9)	-65.5 (94.0)
Week 24: 2 Hours Post-Supper (n=52, 54)	-58.1 (73.2)	-78.0 (82.2)

6. Secondary Outcome

Title	Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 12
Description	Change from Baseine in fasting and postprandial plasma glucose as determined by standardized meal tolerance tests (MTT). Change = mean value at Week 12 minus mean value at Baseline. Time 0 results are for MTT (time 0) and non MTT (implied time 0) subjects.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
0 mins (Fasting) (n=25, 42)	-49.8 (68.6)	-30.5 (58.2)
30 mins (n=6, 6)	-27.9 (65.4)	-44.4 (33.3)
60 mins (n=23, 35)	-58.8 (75.1)	-50.3 (73.2)
90 mins (n=25, 38)	-62.8 (73.5)	-69.5 (65.7)
120 mins (n=26, 40)	-56.3 (71.5)	-77.4 (68.3)
180 mins (n=26, 37)	-49.1 (79.1)	-76.4 (68.8)

7. Secondary Outcome

Title	Change From Baseline in Fasting and Postprandial Plasma Glucose as Determined by Standardized Meal Tolerance Tests at Week 24
Description	Change from Baseline in fasting and postprandial plasma glucose as determined by standardized meal tolerance tests (MTT). Change = mean value at Week 24 minus mean value at Baseline. Time 0 results are for MTT (time 0) and non MTT (implied time 0) subjects.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
0 mins (Fasting) (n=22, 30)	-25.1 (109.5)	-34.8 (64.3)
30 mins (n=1, 7)	-59.5 (0.0)	-86.0 (43.5)
60 mins (n=21, 26)	-64.9 (107.9)	-59.8 (61.9)
90 mins (n=22, 28)	-72.1 (98.9)	-73.6 (54.0)
120 mins (n=23, 29)	-74.2 (95.0)	-75.7 (59.7)
180 mins (n=21, 28)	-64.1 (95.9)	-74.2 (66.2)

8. Secondary Outcome

Title	Change From Baseline in Fasting and Postprandial Lipids as Determined by Standard Meal Tolerance Tests
Description	Change from Baseline in fasting and postprandial lipids at Week 12 and Week 24 as determined by standard meal tolerance tests. Change = value at observation minus value at Baseline. Postprandial = 120 mins after meal.
Time Frame	Baseline, Week 12, Week 24

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
Total cholesterol: Week 12 Fasting (n=60, 79)	-4.4 (21.1)	1.2 (34.9)
Total cholesterol: Week 12 Postprandial(n=22, 33)	-6.8 (14.8)	-6.7 (31.2)
Total cholesterol: Week 24 Fasting (n=51, 59)	-0.2 (31.7)	0.5 (29.9)
Total cholesterol Week 24 Postprandial(n=17, 21)	0.7 (34.3)	-4.7 (29.5)
HDL cholesterol: Week 12 Fasting (n=60, 79)	1.2 (4.5)	1.4 (5.5)
HDL cholesterol: Week 12 Postprandial (n=22, 33)	1.3 (3.5)	1.1 (5.3)
HDL cholesterol: Week 24 Fasting (n=51, 59)	1.1 (5.2)	0.4 (5.9)
HDL cholesterol: Week 12 Postprandial (n=17, 21)	0.0 (5.7)	-0.4 (6.0)
LDL cholesterol: Week 12 Fasting (n=60, 79)	1.3 (19.8)	5.9 (29.3)
LDL cholesterol: Week 12 Postprandial (n=22, 33)	-1.4 (13.3)	-1.5 (26.8)
LDL cholesterol: Week 24 Fasting (n=51, 59)	3.5 (27.0)	5.0 (23.9)
LDL cholesterol: Week 24 Postprandial (n=17, 21)	2.5 (31.3)	-0.7 (19.9)
Triglycerides: Week 12: Fasting (n=60, 79)	-34.7 (59.3)	-30.7 (74.3)
Triglycerides: Week 12 : Postprandial (n=22, 33)	-34.1 (42.8)	-31.6 (71.4)
Triglycerides: Week 24: Fasting (n=51, 59)	-24.3 (59.3)	-24.9 (98.4)
Triglycerides: Week 24: Postprandial (n=17, 21)	-9.5 (45.9)	-17.9 (89.0)

9. Secondary Outcome

Title	Number of Subjects With Change From Baseline in Fasting and Postprandial Markers of Cardiovascular (CV) Risk as Determined by Standardized Meal Tolerance Tests
Description	Cardiovascular risk markers included serum high-sensitivity C-reactive protein (hs-CRP)[mg/L], leptin (ng/mL), adiponectin (ug/mL), and spot urine microalbumin. Change = observation of mean fasting and postprandial markers of cardiovascular risk at Week 12 and Week 24 minus mean Baseline observation.
Time Frame	Week 12, Week 24

Outcome Measure Data

Analysis Population Description

Due to cancellation of the EXUBERA program, too few patients participated to explore the markers of cardiovascular (CV) risks so these markers were not summarized.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	0	0

10. Secondary Outcome

Title	Change From Baseline Weight at Each Visit
Description	Change = mean body weight at observation minus mean body weight at Baseline.
Time Frame	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24

Outcome Measure Data

Analysis Population Description

FAS; LOCF (all visits except Baseline); N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
Week 1 Body weight (n=76, 87)	-0.5 (8.4)	-0.3 (5.9)
Week 2 Body weight (n=80, 90)	0.5 (1.5)	0.9 (1.7)
Week 4 Body weight (n=81, 90)	0.1 (8.5)	0.9 (6.2)
Week 8 Body weight (n=81, 90)	1.3 (3.4)	2.1 (3.1)
Week 12 Body weight (n=81, 90)	0.6 (9.9)	2.3 (3.5)
Week 16 Body weight (n=81, 90)	2.5 (3.0)	2.8 (3.9)
Week 20 Body weight (n=81, 90)	2.4 (3.1)	2.9 (7.0)
Week 24 Body weight (n=81, 90)	1.4 (8.4)	3.8 (4.3)

11. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Lipids
Description	Change from baseline in fasting plasma lipids at Week 12 and Week 24. Change = observation mean minus Baseline mean.
Time Frame	Baseline, Week 12, Week 24

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
Total cholesterol: Week 12 (n=60, 79)	-4.4 (21.1)	1.2 (34.9)
Total cholesterol: Week 24 (n=51, 59)	-0.2 (31.7)	0.5 (29.9)
HDL cholesterol: Week 12 (n=60, 79)	1.2 (4.5)	1.4 (5.5)
HDL cholesterol: Week 24 (n=51, 59)	1.1 (5.2)	0.4 (5.9)
LDL cholesterol: Week 12 (n=60, 79)	1.3 (19.8)	5.9 (29.3)
LDL cholesterol: Week 24 (n=51, 59)	3.5 (27.0)	5.0 (23.9)
Triglycerides: Week 12 (n=60, 79)	-34.7 (59.3)	-30.7 (74.3)
Triglycerides: Week 24 (n=51, 59)	-24.3 (59.3)	-24.9 (98.4)

12. Secondary Outcome

Title	Change From Baseline in Insulin Glargine Dose at Each Visit (Office and/or Phone)
Description	Change from Baseline in insulin glargine at each visit. Change = mean at observation minus mean Baseline observation. Basal dose = injection of basal insulin (IU) (insulin glargine).
Time Frame	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least one dose of study medication; Lispro international units (IU) were converted to milligrams (mg) equivalent; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	88	96
Week 1 (n=69, 77)	8.8 (22.7)	4.3 (8.9)
Week 2 (n=60, 69)	14.1 (24.9)	9.1 (14.0)
Week 4 (n=65, 79)	12.8 (21.2)	14.0 (11.7)
Week 8 (n=65, 73)	16.1 (25.6)	19.2 (15.6)
Week 12 (n=57, 68)	24.9 (26.2)	21.3 (20.7)
Week 16 (n=48, 60)	28.1 (30.7)	24.3 (21.4)
Week 20 (n=50, 50)	31.2 (27.4)	28.5 (31.6)
Week 24 (n=29, 38)	37.1 (33.2)	31.2 (28.1)

13. Secondary Outcome

Title	Baseline Prandial Insulin Dose (at Each Meal) at Each Visit
Description	Dose of inhaled insulin prior to each meal at each visit.
Time Frame	Week 0, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least one dose of study medication; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation.

Arm/Group Title	Exubera®
Arm/Group Description	Weight based initiation dose, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to insulin glargine and oral agents.
Measure Participants	88
Week 0: Pre-breakfast (n=81)	4.14 (1.39)
Week 0: Pre-lunch (n=86)	4.10 (1.37)
Week 0: Pre-dinner (n=87)	4.06 (1.33)
Week 1: Pre-breakfast (n=87)	4.25 (1.45)
Week 1: Pre-lunch (n=87)	4.33 (1.42)
Week 1: Pre-dinner (n=87)	4.35 (1.49)
Week 2: Pre-breakfast (n=87)	4.89 (1.63)
Week 2: Pre-lunch (n=87)	4.94 (1.72)
Week 2: Pre-dinner (n=87)	5.09 (1.82)
Week 4: Pre-breakfast (n=84)	5.44 (2.16)
Week 4: Pre-lunch (n=84)	5.46 (2.32)
Week 4: Pre-dinner (n=84)	5.71 (2.36)
Week 8: Pre-breakfast (n=80)	6.09 (2.93)
Week 8: Pre-lunch (n=80)	6.11 (2.99)
Week 8: Pre-dinner (n=80)	6.41 (3.07)
Week 12: Pre-breakfast (n=74)	6.40 (3.17)
Week 12: Pre-lunch (n=74)	6.51 (3.35)
Week 12: Pre-dinner (n=74)	7.01 (3.67)
Week 16: Pre-breakfast (n=71)	6.69 (3.60)
Week 16: Pre-lunch (n=71)	6.78 (3.82)
Week 16: Pre-dinner (n=71)	7.40 (4.04)
Week 20: Pre-breakfast (n=68)	7.01 (4.06)
Week 20: Pre-lunch (n=68)	7.10 (4.20)
Week 20: Pre-dinner (n=68)	7.58 (4.30)
Week 24: Pre-breakfast (n=66)	7.53 (4.78)
Week 24: Pre-lunch (n=66)	7.70 (4.69)
Week 24: Pre-dinner (n=66)	7.83 (4.81)

14. Secondary Outcome

Title	Number of Subjects With Hypoglycemic Events
Description	Severe event = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable/irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or not measured but clinical manifestations reversed by oral carbohydrates or glucose. Non-severe events = events that were mild-moderate.
Time Frame	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least one dose of study medication; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	88	96
Month 1: Overall (n=88, 96)	38 43.2%	35 36.5%
Month 1: Mild/Moderate (n=88, 96)	38 43.2%	35 36.5%
Month 1: Severe (n=88, 96)	0 0%	0 0%
Month 2: Overall (n=81, 91)	26 29.5%	29 30.2%
Month 2: Mild/Moderate (n=81, 91)	25 28.4%	29 30.2%
Month 2: Severe (n=81, 91)	1 1.1%	0 0%
Month 3: Overall (n=74, 87)	29 33%	38 39.6%
Month 3: Mild/Moderate (n=74, 87)	29 33%	38 39.6%
Month 3: Severe (n=74, 87)	0 0%	0 0%
Month 4: Overall (n=71, 81)	22 25%	28 29.2%
Month 4: Mild/Moderate (n=71, 81)	22 25%	28 29.2%
Month 4: Severe (n=71, 81)	0 0%	0 0%
Month 5: Overall (n=69, 75)	25 28.4%	26 27.1%
Month 5: Mild/Moderate (n=69, 75)	25 28.4%	26 27.1%
Month 5: Severe (n=69, 75)	0 0%	0 0%
Month 6: Overall (n=66, 70)	17 19.3%	21 21.9%
Month 6: Mild/Moderate (n=66, 70)	17 19.3%	21 21.9%
Month 6: Severe (n=66, 70)	0 0%	1 1%

15. Secondary Outcome

Title	Number of Total Hypoglycemic Events
Description	Total number and severity of hypoglycemic events. Severe events = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable or irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or not measured but clinical manifestations reversed by oral carbohydrates or glucose. Non-severe events = events that were mild or moderate.
Time Frame	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least one dose of study medication; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	88	96
Month 1: Overall (n=88, 96)	106	121
Month 1: Mild/Moderate (n=88, 96)	106	121
Month 1: Severe (n=88, 96)	0	0
Month 2: Overall (n=81, 91)	73	120
Month 2: Mild/Moderate (n=81, 91)	72	120
Month 2: Severe (n=81, 91)	1	0
Month 3: Overall (n=74, 87)	103	114
Month 3: Mild/Moderate (n=74, 87)	101	113
Month 3: Severe (n=74, 87)	0	0
Month 4: Overall (n=71, 81)	57	80
Month 4: Mild/Moderate (n=71, 81)	57	80
Month 4: Severe (n=71, 81)	0	0
Month 5: Overall (n=69, 75)	70	89
Month 5: Mild/Moderate (n=69, 75)	70	88
Month 5: Severe (n=69, 75)	0	0
Month 6: Overall (n=66, 70)	35	48
Month 6: Mild/Moderate (n=66, 70)	35	47
Month 6: Severe (n=66, 70)	0	1

16. Secondary Outcome

Title	Treatment Exposure for Hypoglycemic Subjects at Each Interval of the Study: Number of Subject Months of Treatment
Description	Subject months of treatment = number of days from start of treatment to last day of active treatment + 1 day lag (total number of subjects treated * days treated), including off-drug time)/30.44. Severity: severe = subject unable to treat self, had at least 1 neurological symptom (memory loss, confusion, uncontrollable/irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams/deciliter; or not measured but clinical manifestations were reversed by oral carbohydrates or glucose. Non-severe events = events that were mild or moderate.
Time Frame	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least one dose of study medication; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	88	96
Month 1: Overall (n=88, 96)	85.3	92.9
Month 1: Mild/Moderate (n=88, 96)	85.3	92.9
Month 1: Severe (n=88, 96)	85.3	92.9
Month 2: Overall (n=81, 91)	78.3	88.8
Month 2: Mild/Moderate (n=81, 91)	78.3	88.8
Month 2: Severe (n=81, 91)	78.3	88.8
Month 3: Overall (n=74, 87)	72.2	85.1
Month 3: Mild/Moderate (n=74, 87)	72.2	85.1
Month 3: Severe (n=74, 87)	72.2	85.1
Month 4: Overall (n=71, 81)	70.4	77.6
Month 4: Mild/Moderate (n=71, 81)	70.4	77.6
Month 4: Severe (n=71, 81)	70.4	77.6
Month 5: Overall (n=69, 75)	68.0	73.6
Month 5: Mild/Moderate (n=69, 75)	68.0	73.6
Month 5: Severe (n=69, 75)	68.0	73.6
Month 6: Overall (n=66, 70)	41.4	43.8
Month 6: Mild/Moderate (n=66, 70)	41.4	43.8
Month 6: Severe (n=66, 70)	41.4	43.8

17. Secondary Outcome

Title	Crude Hypoglycemic Event Rate
Description	Crude event rate = (number of events)/(subject months); severe hypoglycemic events: crude event rate = (number of events)/(100 subject months). Severe = subject unable to treat self, at least 1 neurological symptom (memory loss, confusion, uncontrollable or irrational behavior, difficulty awakening, suspected seizure, loss of consciousness), and blood glucose <= 49 milligrams per deciliter (mg/dL) or unmeasured but clinical manifestestation reversed by oral carbohydrates or glucose. Non-severe events = mild-moderate.
Time Frame	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6

Outcome Measure Data

Analysis Population Description

Safety population; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	88	96
Month 1: Overall (n=88, 96)	1.2	1.3
Month 1: Mild/Moderate (n=88, 96)	1.2	1.3
Month 1: Severe (n=88, 96)	0.0	0.0
Month 2: Overall (n=81, 91)	0.9	1.4
Month 2: Mild/Moderate (n=81, 91)	0.9	1.4
Month 2: Severe (n=81, 91)	1.3	0.0
Month 3: Overall (n=74, 87)	1.4	1.3
Month 3: Mild/Moderate (n=74, 87)	1.4	1.3
Month 3: Severe (n=74, 87)	0.0	0.0
Month 4: Overall (n=71, 81)	0.8	1.0
Month 4: Mild/Moderate (n=71, 81)	0.8	1.0
Month 4: Severe (n=71, 81)	0.0	0.0
Month 5: Overall (n=69, 75)	1.0	1.2
Month 5: Mild/Moderate (n=69, 75)	1.0	1.2
Month 5: Severe (n=69, 75)	0.0	0.0
Month 6: Overall (n=66, 70)	0.8	1.1
Month 6: Mild/Moderate (n=66, 70)	0.8	1.1
Month 6: Severe (n=66, 70)	0.0	2.3

18. Secondary Outcome

Title	Change From Baseline in Patient Treatment Satisfaction (as Assessed by Patient Satisfaction With Insulin Treatment [PSIT] Questionnaire)
Description	Patient Satisfaction with insulin treatment Questionnaire (PSIT): 15-item self administered questionnaire that measures global satisfaction and two domains (subscales): convenience/ease of use and social comfort in people with type 1 and type 2 diabetes. 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). The scoring of responses to each item is analyzed so that a higher item score indicates more satisfaction. Change = mean Patient Satisfaction of Insulin Treatment (PSIT) score at observation minus mean score at Baseline.
Time Frame	Week 4, Week 24

Outcome Measure Data

Analysis Population Description

Due to cancellation of the EXUBERA program descriptive statistics for the Patient Satisfaction of Insulin Treatment (PSIT) Questionnaire were not provided.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	0	0

19. Secondary Outcome

Title	Change in Patient Treatment Satisfaction (as Assessed by Patient Satisfaction With Insulin Treatment [PSIT] Questionnaire) From Week 4 to Week 24
Description	Patient Satisfaction with insulin treatment Questionnaire (PSIT): 15-item self administered questionnaire that measures global satisfaction and two domains (subscales): convenience/ease of use and social comfort in people with type 1 and type 2 diabetes. 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). The scoring of responses to each item is analyzed so that a higher item score indicates more satisfaction. Change = difference in mean Patient Satisfaction with Insulin Treatment (PSIT) score from Week 4 to Week 24.
Time Frame	Week 4, Week 24

Outcome Measure Data

Analysis Population Description

Due to cancellation of the EXUBERA program descriptive statistics for the Patient Satisfaction of Insulin Treatment (PSIT) Questionnaire were not provided.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	0	0

20. Secondary Outcome

Title	Change From Baseline in 24-hour Mean Glucose Values Measured by Continuous Glucose Monitoring System (CGMS)
Description	Mean of 24-hour Continuous Glucose Monitoring (CGMS) glucose values. Change from Baseline = mean at observation minus mean Baseline value.
Time Frame	Baseline, Week 12, Week 24

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
Week 12 (n=19, 16)	-30.4 (44.3)	-33.0 (41.9)
Week 24 (n=17, 13)	-19.4 (43.7)	-23.4 (43.1)

21. Secondary Outcome

Title	Change From Baseline in Standard Deviation of 24-hour Glucose Values Measured by Continuous Glucose Monitoring System (CGMS)
Description	Mean change in standard deviation of all blood glucose values within 24-hour period. Change = mean at observation minus mean at Baseline.
Time Frame	Baseline, Week 12, Week 24

Outcome Measure Data

Analysis Population Description

FAS; N=number of subjects with evaluable data; n=number of subjects with evaluable data at observation: Exubera, Lispro, respectively.

Arm/Group Title	Exubera®	Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.	Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
Measure Participants	81	90
Week 12 (n=19, 16)	-3.4 (25.5)	2.3 (20.9)
Week 24 (n=17, 13)	-3.6 (22.4)	-0.9 (14.3)

Adverse Events

Adverse Event Reporting Description	Number of participants at risk for serious and other adverse events was determined by the number of participants who took at least one dose of study drug.
Arm/Group Title	Exubera®		Insulin Lispro
Arm/Group Description	Weight based initiation dose of Exubera® (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); approx. 0.05 mg/kg per meal, three times per day [TID]), and individually titrated doses per subject's blood glucose in addition to insulin glargine and oral agents.		Weight based initiation dose of insulin-lispro (total daily dose: body weight in kilograms (kg) x 0.15 milligrams per kilogram (mg/kg); divided into 3 equal preprandial doses [before breakfast, lunch, and dinner], and individually titrated doses per subject's blood glucose, in addition to insulin glargine and oral agents. The approximate insulin-lispro dose in units was prescribed based on the calculated dose of Exubera® (conversion from milligrams (mg) of Exubera® to international units (IU) of insulin-lispro was approx. 3:1).
All Cause Mortality
	Exubera®		Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Exubera®		Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/88 (3.4%)		3/96 (3.1%)
Gastrointestinal disorders
Ileus	0/88 (0%)		1/96 (1%)
Infections and infestations
Labyrinthitis	0/88 (0%)		1/96 (1%)
Injury, poisoning and procedural complications
Meniscus lesion	1/88 (1.1%)		0/96 (0%)
Ligament rupture	1/88 (1.1%)		0/96 (0%)
Subdural haematoma	0/88 (0%)		1/96 (1%)
Medical device complication	1/88 (1.1%)		0/96 (0%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/88 (1.1%)		0/96 (0%)
Other (Not Including Serious) Adverse Events
	Exubera®		Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/88 (77.3%)		67/96 (69.8%)
Cardiac disorders
Palpitations	3/88 (3.4%)		5/96 (5.2%)
Eye disorders
Vision blurred	4/88 (4.5%)		5/96 (5.2%)
Gastrointestinal disorders
Diarrhoea	0/88 (0%)		6/96 (6.3%)
General disorders
Hunger	1/88 (1.1%)		5/96 (5.2%)
Infections and infestations
Influenza	5/88 (5.7%)		4/96 (4.2%)
Nasopharyngitis	5/88 (5.7%)		3/96 (3.1%)
Sinusitis	5/88 (5.7%)		3/96 (3.1%)
Upper respiratory tract infection	9/88 (10.2%)		9/96 (9.4%)
Metabolism and nutrition disorders
Hypoglycaemia	58/88 (65.9%)		59/96 (61.5%)
Nervous system disorders
Dizziness	9/88 (10.2%)		15/96 (15.6%)
Headache	8/88 (9.1%)		7/96 (7.3%)
Tremor	10/88 (11.4%)		12/96 (12.5%)
Respiratory, thoracic and mediastinal disorders
Cough	8/88 (9.1%)		1/96 (1%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	9/88 (10.2%)		12/96 (12.5%)

Limitations/Caveats

Due to cancellation of the EXUBERA program the sample size was too small to adequately address the inferential objectives of this study. Descriptive statistics for the PSIT Questionnaire and the markers of cardiovascular risk were not provided.

More Information

Certain Agreements

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

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