Inhaled insulin: a model for pulmonary systemic absorption?

The European Union recently approved a form of insulin intended to be inhaled. This innovative presentation has the potential to partially or completely replace the injections and thus facilitate starting insulin therapy which is considered with apprehension and often differed. On this occasion, we reviewed the issues raised by this pulmonary route for systemic absorption (anatomical and cytological limits, cellular mechanisms, relevant physical parameters, facilitating chemical cofactors, role of tobacco smoking and of common respiratory diseases). The pharmacokinetics of inhaled and injectable insulins are comparable, apart from an appreciably faster absorption of the former, and both show the same intra-individual variability. The total bioavailability is definitely lower with the inhaled route but is notably increased in smokers. These characteristics can vary according to the inhalation system used. A frequent induced cough, the increase in circulating anti-insulin antibodies, and a potentially higher cost are not really determining obstacles. The indications will have to be clearly specified and the long-term innocuousness of repeated inhalation of such a mitogen, especially in children and former smokers, remains to be fully proven.