Assessment of long-term immunological and pulmonary safety of inhaled human insulin with up to 24 months of continuous therapy.

Background: This study was performed to characterize the long-term safety and efficacy of inhaled human insulin (EXU; Exubera* (insulin human [rDNA origin]) Inhalation Powder). Scope: Patients with type 1 or type 2 diabetes (N = 1290) who had successfully completed one of six controlled EXU open-label trials elected to receive open-label treatment with EXU for up to 3 years, after which they were randomized to discontinue EXU or to continue therapy for 6 months, then discontinue. Immunologic safety was assessed by insulin antibody (IAb) binding, and pulmonary safety was assessed by tests for forced expiratory volume in 1 second (FEV1) and carbon monoxide diffusing capacity (DLCO). In addition, changes over time in IAbs were compared with changes in FEV1, DLCO, hypoglycemia, and efficacy. Findings: Antibody binding increased in patients with either type 1 or type 2 diabetes after initiation of EXU and plateaued within 6 -12 months (increases were higher in patients with type 1 diabetes than in patients with type 2 diabetes). Decreases in FEV1 occurred primarily during the first 3 -6 months of EXU therapy. Among adult patients in the All Subjects set, the mean (+/- SE) annualized rate of decline in FEV1 was -0.053 +/- 0.007 liters/year (95% CI, -0.065, -0.040) in adult patients with type 1 diabetes, and -0.076 +/- 0.005 liters/ year (95% CI, -0.085, -0.067) in patients with type 2 diabetes. Changes in DLCO occurred primarily during the first 3 -6 months of EXU therapy. Among adult patients, in the All Subjects set, the mean (+/- SE) annual decline in DLCO was -0.738 +/- 0.097 mL/min/ mmHg/year (95% CI, -0.927, -0.548) and -0.688 +/- 0.082 mL/min/mmHg/year (95% CI, -0.849, -0.527) in patients with type 1 and type 2 diabetes, respectively. Antibody binding did not correlate with changes in glycemic control, lung function, dose, or hypoglycemia. Following discontinuation of EXU, IAbs decreased to near baseline levels. Conclusion: These results are consistent with other trials showing long-term maintenance of safety and efficacy of EXU despite insulin antibody formation and small treatment group differences in pulmonary function. A limitation of the study was the lack of a comparator therapy.