A SIX MONTH, OPEN-LABEL OUTPATIENT, RANDOMIZED PARALLEL GROUP TRIAL ASSESSING THE IMPACT OF DRY POWDER INHALED INSULIN (EXUBERA®) ON GLYCEMIC CONTROL COMPARED TO INSULIN GLARGINE (LANTUS®) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS WHO ARE POORLY CONTROLLED ON A COMBINATION OF TWO OR MORE ORAL AGENTS

INTERVENTION: Trade Name: Exubera® Pharmaceutical Form: Inhalation powder, pre-dispensed INN or Proposed INN: Insulin Human CAS Number: 11061-68-0 Other descriptive name: CP 464,005 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1- Trade Name: Exubera® Pharmaceutical Form: Inhalation powder, pre-dispensed INN or Proposed INN: Insulin Human CAS Number: 11061-68-0 Other descriptive name: CP 464,005 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 3- Trade Name: Lantus® Pharmaceutical Form: Solution for injection INN or Proposed INN: Insulin glargine CAS Number: 160337-95-1 Concentration unit: IU/ml international unit(s)/millilitre Concentration type: equal Concentration number: 100-, CONDITION: Diabetes Mellitus type II (non insulin dependent) ; MedDRA version: 8.1, Level: LLT, Classification code 10012601, Term: Diabetes mellitus, PRIMARY OUTCOME: Main Objective: The primary objective of the study is to demonstrate non-inferiority of dry powder inhaled insulin (Exubera®) compared to insulin Glargine (Lantus®) in terms of glycemic control (HbA1c) after 26 weeks of treatment.; Primary end point(s): The primary endpoint is the change from baseline to HbA1c measured at week 26 (approx. 6 months) after treatment. Secondary Objective: Secondary objectives of the study are to demonstrate superiority of inhaled insulin over insulin Glargine on the following endpoints: change of fasting glucose and postprandial glucose excursions from baseline to end of the treatment period, the percentage of subjects who have an HbA1c of less than 6.5%, 7.0%, or 8.0% at; the end of the treatment period, rates of overall and nocturnal hypoglycemia, changes in body weight and BMI, glucose excursions over 24 hours in a subset of subjects, and patient reported outcomes at week 26 compared to baseline. Additional secondary objectives are changes in urinary free 8 iso-prostaglandin F2a in a subset of patients, high sensitive C-reactive protein, interleukin 6 (IL-6), thrombin-antithrombin complexes (tat-complexes), and soluble tissue factor from baseline to end of the treatment period., INCLUSION CRITERIA: Male and female subjects meeting all of the following criteria will be considered for enrollment into the study. 1. Age = 30 years with a diagnosis of type 2 diabetes mellitus made = 6 months prior to study entry, as defined by the American Diabetes Association (Diabetes Care 25: S5-S20, 2002). 2. Screening HbA1c = 7.0% 3. Currently treated on a stable dose of at least 2 oral hypoglycemic agents which must include combinations of sulfonylureas and metformin for at least 3 months prior to study entry. If a subject on a non-sulfonylurea secretagogue can be switched to glimepiride 2 mg at visit 2, they may be screened. Treatment with thiazolidinediones is permitted in addition to the sulfonylurea and metformin where concurrent treatment with insulin is permitted. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years)