AIR^® Inhaled Insulin in Subjects with Chronic Obstructive Pulmonary Disease: Pharmacokinetics, Glucodynamics, Safety, and Tolerability

Abstract

OBJECTIVE--- In this open-label, randomized, crossover study, pharmacokinetic and glucodynamic responses were compared in healthy subjects versus subjects with moderate COPD, following administration of 12 units-equivalent AIR^® Inhaled Insulin versus 12 units subcutaneous (SC) insulin lispro.

RESEARCH DESIGN AND METHODS--- Three nonsmoking groups (n=15 each)---healthy subjects (baseline mean ± SD: aged 38±13 years, FEV₁ 4.06±1.04 L), subjects with chronic bronchitis (aged 53±9 years, FEV₁ 2.14±0.60 L), and subjects with pulmonary emphysema (aged 58±6 years, FEV₁ 1.67±0.61 L)---were randomly assigned to one of three treatment sequences. Three euglycemic glucose clamp procedures were performed.

RESULTS--- In subjects with chronic bronchitis and emphysema, AIR Inhaled Insulin administration resulted in reduced insulin exposure (AUC_0-t') (55.7%, P = 0.13 and 78.5%, P < 0.001, respectively) and reduced total insulin effect (GIR_tot) (60.4%, P < 0.01 and 67.1%, P < 0.01, respectively) relative to healthy subjects. SC insulin lispro administration resulted in similar responses across study groups for insulin exposure and metabolic effect. Intra-subject pharmacokinetic and glucodynamic variability ranged from 17--52% across groups. No significant differences were shown for pre- and post-clamp pulmonary function tests. During clamps, FEV₁ and FVC declined modestly in both COPD groups with no difference between AIR Insulin and SC insulin lispro.

CONCLUSIONS--- Short-time exposure with AIR Inhaled Insulin was well tolerated by COPD subjects, showing similar time-exposure and time-action profiles, but with reduced insulin absorption and metabolic effect compared with healthy subjects. Further clinical evaluation is warranted in patients with comorbid diabetes and COPD.