Abstract

Objective: This study evaluated pharmacokinetic and glucodynamic responses to AIR^® inhaled insulin relative to subcutaneous insulin lispro, safety, pulmonary function, and effects of salbutamol co-administration.

Research Design And Methods: Healthy, mild asthmatic, and moderate asthmatic subjects (n=13/group; age 19–58 years; nonsmoking; nondiabetic) completed this phase I, open-label, randomized, crossover euglycemic clamp study. Subjects received 12U-equivalent AIR Insulin, or 12U subcutaneous insulin lispro, or salbutamol+AIR Insulin (moderate asthma group only) prior to clamp.

Results: AIR Insulin exposure was reduced 34% and 41% (both P<0.01) in asthmatic subjects (AUC_0-t', 24.0 and 21.1 nmol·min/L in mild and moderate subjects, respectively), relative to healthy subjects (35.2 nmol·min/L). Glucodynamic effects were similar in healthy and mild asthmatic subjects (G_tot 38.7 and 23.4 g respectively, P=0.16), and reduced in moderate asthmatic subjects (G_tot 10.7 g). Salbutamol pretreatment (moderate asthmatic subjects) improved bioavailability. AIR insulin had no discernable effect on pulmonary function. AIR Insulin adverse events (cough, headache, and dizziness) were mild-to-moderate in intensity and have been previously reported or are typical of studies involving glucose clamp procedures.

Conclusions: This study suggests that pulmonary disease severity and asthma treatment status influence the metabolic effect of AIR Insulin in individuals with asthma, but do not affect AIR Insulin pulmonary safety or tolerability. In view of the potential interactions between diabetes treatment and pulmonary status it is prudent to await the results of ongoing clinical trials in diabetic patients with comorbid lung disease before considering the use of inhaled insulin in such patients.