Pulmonary safety of inhaled insulins: a review of the current data

The availability of non-invasive insulin delivery options for patients with diabetes may encourage earlier insulin use, and thus improve glycemic control and help reduce the diabetes burden. Pulmonary insulin delivery is the most promising alternative with several inhaled insulin systems in development, and the inhaled human insulin Exubera* (insulin human [rDNA origin] Inhalation Powder) has been recently approved in the United States and in the European Union for the treatment of adults with type 1 or type 2 diabetes. Pulmonary function is an important aspect of the safety profile for compounds delivered via the lungs. Pulmonary function with Exubera has been extensively investigated in several completed and ongoing Phase 3 studies conducted in patients with type 1 or type 2 diabetes. A small, consistent but clinically non-significant decrease in pulmonary function, occurs early, does not progress during 2 years of continuous therapy, and is reversible after discontinuation. A mild, transient cough occurring after inhalation of Exubera is the most common respiratory adverse event observed. Impaired lung function in asthma and chronic obstructive pulmonary disease may modify the absorption of Exubera, whereas active smoking is associated with increased absorption increasing the risk of hypoglycemia. Limited information is available regarding the pulmonary safety of other inhaled insulins, but comprehensive pulmonary studies are anticipated in the future. In preparing this article, the authors searched for references to inhaled insulin in the Medline database and in congress abstracts from 1998 to 2006.