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

ABSTRACT

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).

* Pfizer Inc, New York, NY, USA

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 (DL_CO). In addition, changes over time in IAbs were compared with changes in FEV₁, DL_CO, 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 DL_CO 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 DL_CO 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.

Key words: :

• Efficacy
• Inhaled insulin
• Safety
• Type 1 diabetes
• Type 2 diabetes

Acknowledgements

Declaration of interest: This study was funded by Pfizer Inc. Editorial support was provided by Mark Poirier of PAREXEL and was funded by Pfizer Inc.

Notes

* Pfizer Inc, New York, NY, USA

* Pfizer Inc, New York, NY, USA