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 I 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 190% 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(-1) with SC insulin (nonsignificant mean difference -0.150 ml (.) min(-1) (.) mmHg(-1) (.) year [-0.310 to 0.011]) forDL(CO). The mean annual rates of change in FEV, 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 FEV, developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except 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 sustaine 13. (adjusted mean treatment difference in change from baseline AIC at month 24 0.25 - 0.07% [0. 13-0.371). 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 Body 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 f or insulin in adult patients with type I diabetes are small, develop early, and are nonprogressive up to 2 years of therapy.