A Clinical Trial Comparing the Efficacy and Safety of Exubera® and Lantus®

Change (measured as percent): HbA1c at observation minus HbA1c at baseline. Primary objective to demonstrate non-inferiority of inhaled insulin compared to insulin glargine for glycemic control after 26 weeks of treatment not attainable due to early termination of study; analyses were descriptive and graphical.

Change (measured as percent) from baseline calculated as HbA1c at observation minus HbA1c at baseline.

Number of subjects with glycemic control HbA1c measurement of < 6.5 % at observation.

Number of subjects with glycemic control HbA1c measurement of < 7.0 % at observation.

Number of subjects with glycemic control HbA1c measurement of < 8.0 % at observation.

FPG measured as milligrams/deciliter (mg/dl). Change from baseline calculated as FPG at observation minus FPG at baseline.

Blood glucose (BG) self-monitored by subject at home; measured at least once between Visits 2, 3 and between Visits 8, 9 (8-point: fasting, pre-meal, post-meal, bedtime, 2:00 am); between each visit: Visit 3 to 8 (7-point: fasting, post-meal, pre-lunch, pre-dinner, bedtime). Post-meal: 2-hour period after breakfast, lunch, dinner. Change: average overall absolute, pre-meal, and post-meal blood glucose = HBGM at observation minus HBGM at baseline; pre-meal to post-meal blood glucose = HBGM at post-meal minus HBGM at pre-meal.

Number of subjects with hypoglycemic events by severity. Severe hypoglycemia: subject unable to treat self; exhibits a neurological symptom; and blood glucose <=2.72 mmol/L or blood glucose not measured but symptoms reversed with food intake, SC glucagon, or intravenous glucose. If all 3 criteria not met, hypoglycemia defined as mild or moderate.

Number of events of nocturnal hypoglycemia, incidence: midnight to 6:00 am. Hypoglycemia: characteristic symptoms of hypoglycemia with no blood glucose check; resolved with food intake, SC glucagon, or intravenous (IV) glucose; or symptoms with glucose <3.27 mmol/L (59 mg/dL); or any glucose measurement <=2.72 mmol/L (49 mg/dl). Severity of nocturnal glycemia not summarized.

Change from baseline calculated as body weight at observation minus body weight at baseline.

BMI measured as kilograms per meter squared (kg/m2). Change calculated as BMI at observation minus BMI at baseline.

Number of subjects discontinued due to signs and symptoms of persistent hyperglycemia or HbA1c > 12.0 % or frequent and unexplained severe hypoglycemic events (> 3 events per month for 2 or more months); subject's HbA1c not < = 7 % at Week 12.

Subject reported outcomes for Diabetes Treatment Satisfaction Questionnaire-Status (DTSQs), DTSQ-change, Patient Satisfaction with Insulin Therapy-16 item, Mental Health Inventory-17 item, and Euro Quality of life 5-Dimensions (EuroQol 5-D) Questionnaire not summarized due to cancellation of Exubera® program.

The mean of the 24-hour mean and the mean of the 24-hour standard deviation (SD) (variability around the average glucose concentration) calculated on glucose values (mg/dl) collected during inpatient evaluation of glycemic stability. Interstitial glucose assessed at 5 minute intervals starting pre-supper on Day 1 of evaluation; ending on Day 3 pre-breakfast. Analysis is on data generated between 6:00 am on Day 2 and 6:00 am on Day 3.

Change from baseline in CV biomarker hs-CRP (milligrams per deciliter [mg/dl]) calculated as hs-CRP at observation minus hs-CRP at baseline.

Change from baseline in IL-6 (picograms per milliliter [pg/ml]) calculated as IL-6 at observation minus IL-6 at baseline.

Change from baseline in tat-complexes (nanograms per milliliter [ng/ml]) calculated as tat-complexes at observation minus tat-complexes at baseline.

Change from baseline in soluble tissue factor (pg/ml) calculated as STF at observation minus STF at baseline.

Urinary free 8-iso prostaglandin F2-alpha (α): compare glucose fluctuations and activation of oxidative stress as assessed by urinary isoprostanes in a subset of subjects randomized to either Exubera® or subcutaneous insulin glargine. The substudy was offered to all subjects. Data not summarized due to cancellation of Exubera® program.