Inhaled insulin for the treatment of diabetes: projects and devices.

A non-invasive alternative to insulin injections would represent a major improvement for Type 1 and 2 insulin-treated patients. The lung is the only route which allows bio-availability of insulin, approaching 10% without absorption enhancers. However, the reproducibility of the plasma response to the pulmonary insulin is similar to subcutaneous insulin analogues, that is to say, relatively poor. In the Exubera Project, the device is a dry powder inhaler. The insulin powder (Aventis) is packaged into a single dose blister containing 1 or 3 mg; the 1 mg blister corresponding to approximately 3 U of insulin. Phase II studies have shown similar efficacy than regular insulin. Data are available on 328 Type 1 and 309 Type 2 patients after 6 months of Phase III trials. The inhaled insulin group developed increased insulin antibodies. A total of 25% of the patients experienced cough after inhalation. The number of overall and severe hypoglycaemic episodes were similar in the two groups. Pulmonary function tests remained stable and normal except for minor reductions of carbon monoxide diffusion capacity. The AERx IDMS system is a microprocessor-controlled, aqeous mist inhaler. The insulin (regular 100 U/ml, Novo Nordisk) is delivered by 1 U increments. The clinical experience reported with this system so far is limited to 107 Type 2 insulin-treated patients. The results are similar to those obtained in the Exubera trials. In the Alkermes project, large, porous, regular insulin of low-mass density have been developed by the Advanced Inhalation Project. Results from human studies in normal subjects show similar pharmacokinetics as the two other devices above. Other projects seem less advanced than the projects cited above e.g., Aerodos and Oralin. Current clinical experience with inhaled insulin seems promising. It represents currently the only viable non-invasive alternative to insulin injections. However, long-term local tolerance of the pulmonary tissue is a crucial issue.