Inhaled insulin: safety

Clinical studies of inhaled insulins suggest that pulmonary delivery is well tolerated, with a level of safety comparable to that of subcutaneous (SC) insulin. Questions about the safety of Exubera(R) focus primarily on the lungs, which are probably exposed to two to three times more insulin than an SC injection site. Pulmonary function tests (forced expiratory volume in 1 s and carbon monoxide-diffusing capacity) are routinely included as primary endpoints in Exubera( clinical trials. Completed phase 2 and 3 studies up to 4 years in duration indicate that the differences over time in pulmonary function changes between patients treated with Exubera(R) and control patients are small, non-progressive, clinically insignificant and reverse after discontinuation of Exubera(R) therapy. However, it would be useful to understand the physiologic mechanisms responsible for these changes, and ongoing studies should continue to monitor the effects of inhaled insulin on pulmonary function and other parameters in patients with diabetes. In clinical trials of patients with type 1 or 2 diabetes who were treated with Exubera(R), the only significant clinical adverse effect was cough. This was generally characterized as mild to moderate in severity, decreased over time and was not associated with declines in lung function. Thus, insulin administration via the lung appears to be generally safe in patients with type 1 or 2 diabetes.