Objective: This study assessed pulmonary safety following discontinuation and readministration of inhaled human insulin {Exubera [EXU] [Pfizer Inc., New York, NY] (insulin human [recombinant DNA origin]) inhalation powder} in adults with type 2 diabetes (T2DM).
Methods: Patients were randomized to receive EXU (n = 316) or subcutaneous (SC) insulin (n = 311) for 2 years (comparative phase), followed by 6 months of SC insulin (washout phase) and 6 months of original therapy (readministration). Highly standardized lung function tests were performed throughout all phases.
Results: Small, nonprogressive treatment group differences were observed to occur early during the comparative phase for parameters such as change from baseline for forced expiratory volume in 1 s (FEV(1)) and carbon monoxide diffusing capacity (DL(CO)). These differences resolved during washout and recurred to the same small magnitude during readministration. Both treatment groups maintained similar glycemic control and hypoglycemic event rates. In the EXU group, insulin antibody (IAb) levels reached a plateau at 9 months, declined to near baseline levels during washout, and increased during readministration to levels observed in the comparative phase.
Conclusions: FEV(1) and DL(CO) changes observed during discontinuation and readministration of EXU therapy were consistent with a reversible, nonprogressive, and nonstructural pathologic effect on lung function in adults with T2DM. EXU readministration was not associated with an augmented IAb response.
Trial registration: ClinicalTrials.gov NCT00136916.