Safety and efficacy of inhaled human insulin (exubera) during discontinuation and readministration of therapy in adults with type 2 diabetes: a 3-year randomized controlled trial.
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.
Rosenstock
Julio
J
Dallas Diabetes and Endocrine Center, Texas 75230, USA. juliorosenstock@dallasdiabetes.com
Cefalu
William T
WT
Hollander
Priscilla A
PA
Klioze
Sol S
SS
Reis
Joann
J
Duggan
William T
WT
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D012129:Respiratory Function Tests; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin