This Study Is To Determine If Inhaled Insulin Is Effective In Treating Type 2 Diabetes Mellitus

• Percentage of Subjects Achieving Glycemic Control (HbA1c < 6.5%) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
• Percentage of Subjects Achieving Glycemic Control (HbA1c < 7.0%) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
• Percentage of Subjects Achieving Glycemic Control (HbA1c < 8.0%) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in Fasting Plasma Glucose at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in Lipids at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in CV Biomarkers Adiponectin and Apolipoprotein B (ApoB) at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in 24-Hour Continuous Glucose Monitoring System (CGMS) Glucose Values at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in Mean Standard Deviation (SD) of 24-Hour Glucose Values Measured by CGMS at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Number of Subjects With Hypoglycemic Events [ Time Frame: Months 1 to 7 ] [ Designated as safety issue: Yes ]
• Number of Total Hypoglycemic Events [ Time Frame: Months 1 to 7 ] [ Designated as safety issue: Yes ]
• Number of Total Subject Months of Treatment [ Time Frame: Months 1 to 7 ] [ Designated as safety issue: Yes ]
• Crude Hypoglycemic Event Rate [ Time Frame: Months 1 to 7 ] [ Designated as safety issue: Yes ]
• Number of Nocturnal Hypoglycemic Events [ Time Frame: Months 1 to 7 ] [ Designated as safety issue: Yes ]
• Change From Baseline in Body Weight at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in Body Mass Index (BMI) at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
• Change From Baseline in Diabetes Treatment Satisfaction Questionnaire-Status, Diabetes Treatment Satisfaction Questionnaire-Change, Diabetes-39, Mental Health Inventory-17, and SF-36 Vitality Domain Questionnaire [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]

• Secondary endpoints include the following at week 26:
• Proportion of patients achieving HbA1c < 6.5%
• Proportion of patients achieving HbA1c < 7.0
• Proportion of patients achieving HbA1c < 8.0%
• Change from baseline in fasting plasma glucose level
• Change from baseline in postprandial blood glucose excursions as measured by 8-point profiles and as determined by standardized meal tolerance tests
• Change from baseline in fasting and postprandial plasma glucose, lipids (such as total cholesterol, HDL-c, LDL-c, triglycerides) and CV biomarkers (such as hs-CRP, leptin, adiponectin and apoB and spot urine microalbumin)
• Change from baseline in 24-hour mean glucose values, and glycemic variability measured by CGMS
• Incidence and severity of hypoglycemia
• Incidence and severity of nocturnal hypoglycemia
• Change from baseline in body weight and body mass index (BMI)
• Proportion of patients who discontinue due to insufficient clinical response
• Incidence of clinical adverse events
• Change from baseline in treatment satisfaction, diabetes related quality of life, mental health and energy/vitality
• Characterization of a 24-hour glucose profile in a subset of patients

This study is to determine if inhaled insulin is effective in treating type 2 diabetes mellitus.

• Drug: Insulin glargine
  Insulin glargine, label instruction initiation dose (10 units), and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents.
• Drug: Inhaled Insulin (Exubera)
  Initiation dose of one mg per meal, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents.

• Active Comparator: Insulin glargine
  Insulin glargine, label instruction initiation dose (10 units), and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents.
  Intervention: Drug: Insulin glargine
• Experimental: Exubera
  Initiation dose of one mg per meal, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents.
  Intervention: Drug: Inhaled Insulin (Exubera)

Inclusion Criteria:

• Age > 30 years and ≤ 75 years with a diagnosis of type 2 diabetes mellitus made > 6 months prior to study entry
• Screening HbA1c > 7.0%
• Currently treated on a stable dose of at least 2 oral antidiabetic agents for at least 3 months prior to study entry; including a sulfonylurea and/or metformin, and/or a thiazolidinedione

Exclusion Criteria:

Smoking within last 6 months PFTs outside of range

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus currently (last three months) treated with an insulin regimen (alone or with Oral Antidiabetic Agents)
• Active liver disease; significantly-impaired hepatic function, as shown by, but not limited to, alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) or aspartate transaminase (AST) serum glutamic-oxaloacetic transaminase (SGOT) above 2x the upper limit of normal as measured at visit 1. However, patients with elevated ALT >1.5 upper limit of normal as a result of hepatic steatosis are permitted to enter the study.