PURPOSE: To examine the relationship between changes in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) during inhaled human insulin (EXU; Exubera® (insulin human [rDNA origin]) Inhalation Powder) therapy in adults with diabetes mellitus.
METHODS: A retrospective analysis was performed on pooled data from 14 type 1 and type 2 diabetes trials 3 to 24 months in duration with 1893 patients given EXU and 1715 patients given comparator (COMP). Spirometry tests were performed at baseline and at regular intervals until study completion (up to 2 years). Change from baseline FEV1 for each patient was apportioned into that proportional to the change in FVC (ΔFEV1,p) and that disproportional to the change in FVC (ΔFEV1,d) based on the baseline and end-of-study FEV1/FVC ratios.
RESULTS: The distribution of ΔFEV1,p was similar between EXU and COMP, whereas the distribution of ΔFEV1,d for EXU exhibited a small negative shift versus COMP. Importantly, these changes were not driven by outliers. In contrast, in the subset of patients with declines in FEV1 of ≥ 15% from baseline to the end of treatment, the majority of the FEV1 decline was driven by ΔFEV1,p and not ΔFEV1,d in both treatment groups.
CONCLUSION: The decline in FEV1 seen with EXU is driven by small alterations in FEV1/FVC and not FVC, consistent with small changes in airway function and lung emptying. In patients with relatively larger declines in FEV1 the majority of the decline was driven by changes in FVC and not FEV1/FVC, suggesting that EXU is not playing a major role in mediating these larger changes in lung function.
CLINICAL IMPLICATIONS: The changes in lung physiology associated with EXU are consistent with small alterations in airway function and lung emptying.
DISCLOSURE: Richard Riese, No Product/Research Disclosure Information; Employee Employee of Pfizer Inc. who funded this study