Two-year pulmonary safety and efficacy of inhaled human insulin (Exubera) in adult patients with type 2 diabetes

OBJECTIVE - The purpose of this study was to evaluate the 2-year pulmonary safety of inhaled human insulin (Exubera [EXU]) in 635 nonsmoking adults with type 2 diabetes. RESEARCH DESIGN AND METHODS - Patients were randomly assigned to receive prandial EXU or subcutaneous insulin (regular or short-acting) plus basal (intermediate- or long-acting) insulin. The primary end points were the annual rate of decline in forced expiratory volume in 1 s (FEV1) and carbon monoxide diffusing capacity (DLCO). RESULTS - Small differences in FEV1 favoring subcutaneous insulin developed during the first 3 months but did not progress. Adjusted treatment group differences in FEV, annual rate of change were -0.007 1/year (90% CI -0.021 to 0.006) between months 0 and 24 and 0.000 1/year (- 0.016 to 0.016) during months 3-24. Treatment group differences in DLCO annual rate of change were not significant. Both groups sustained similar reductions in A1C by month 24 (last observation carried for-ward) (EXU 7.7-7.3% vs. subcutaneous insulin 7.8-7.3%). Reductions in fasting plasma glucose (FPG) were greater with EXU than with subcutaneous insulin I (adjusted mean treatment difference -12.4 mg/dl [90% CI -19.7 to -5.0]). Incidence of hypoglycemia was comparable in both groups. Weight increased less with EXU than with for a subcutaneous insulin (-1.3 kg [-1.9 to -0.7]). Adverse events were comparable, except higher incidence of mild cough and dyspnea with EXU. CONCLUSIONS - Two-year prandial EXU therapy showed a small nonprogressive difference in FEV1 and comparable sustained A1C improvement but lower FPG levels and less weight gain than seen in association with subcutaneous insulin in adults with type 2 diabetes.