Two-Year Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 1 Diabetes

OBJECTIVE—The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—Patients were randomly assigned to receive EXU (n = 290) or subcutaneous (SC) insulin (n = 290), plus basal (intermediate- or long-acting) insulin. The primary end point was the annual rate of decline in pulmonary function (forced expiratory volume in 1 s [FEV1] and carbon monoxide diffusing capacity [DLCO]). RESULTS—The mean ± SEM annual rates of change between months 0 and 24 were −0.051 ± 0.005 l/year with EXU and −0.034 ± 0.005 l/year with SC insulin (significant mean difference −0.017 ± 0.007 l/year [90% CI −0.028 to −0.005]) for FEV1 and −0.437 ± 0.073 ml · min−1 · mmHg−1 · year−1 with EXU and −0.287 ± 0.065 ml · min−1 · mmHg−1 · year−1with SC insulin (nonsignificant mean difference −0.150 ml · min−1 · mmHg−1 · year−1 [−0.310 to 0.011]) for DLCO. The mean annual rates of change in FEV1 between months 3 and 24 were −0.041 ± 0.005 and −0.031 ± 0.006 l/year in the EXU and SC insulin groups, respectively (nonsignificant mean difference −0.011 l/year [−0.023 to 0.002]), indicating that the significant difference between the treatment groups in FEV1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1%) that decreased to 1.3% by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 ± 0.07% [0.13–0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with SC insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0.67 [0.57–0.79]). Body weight increased to a significantly lesser extent with EXU (adjusted mean treatment difference −1.25 ± 0.36 kg [−1.85 to −0.66]). CONCLUSIONS—Treatment group differences in lung function between EXU and SC insulin in adult patients with type 1 diabetes are small, develop early, and are nonprogressive for up to 2 years of therapy.