Two-Year Pulmonary Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients with Type 2 Diabetes

Abstract

Objective: 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 (SC) 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 (DL_CO).

Results: Small differences in FEV₁ favoring SC insulin developed during the first 3 months, but did not progress. Adjusted treatment group differences in FEV₁ annual rate of change were –0.007 l/y (90% CI, –0.021 to +0.006) between months 0-24 and 0.000 l/y (90% CI, –0.016 to +0.016) during months 3-24. Treatment group differences in DL_CO annual rate of change were not significant. Both groups sustained similar reductions in A1C by Month 24 LOCF (EXU: 7.7% to 7.3% vs SC insulin: 7.8% to 7.3%). Reductions in fasting plasma glucose (FPG) were greater with EXU than SC insulin (adjusted mean treatment difference –12.4mg/dl, 90% CI –19.7 to –5.0). Incidence of hypoglycemia was comparable in both groups. Weight increased less with EXU than with SC insulin (adjusted mean treatment difference –1.3kg, 90% CI –1.9 to –0.7). Adverse events were comparable, except for a 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 SC insulin in adults with type 2 diabetes.