Inhaled Insulin and the Dream of a Needle-Free Insulin Application

A few years after the discovery of insulin, [Heubner et al. (1924)] and [Gänsslen (1925)] already published studies on insulin administration by inhalation in Klinische Wochenschrift (see Fig. [1]). Now, 80 years later, the dream of a needle-free insulin delivery system appears to be becoming reality. On March 4, 2004, Pfizer Inc. and Aventis Pharma publicly announced that they had submitted an application for a European license for the inhaled insulin preparation, Exubera®, and that the application had been accepted by the Agency for the Evaluation of Medicinal Products (EMEA), the regulatory authority of the European Union. Although this does not necessarily mean that inhaled human insulin will be available soon, the procedures for a European license are now underway. On March 18, 2004 the “Exubera End of Study Meeting” for the studies 1001 and 1002 took place in Monte Carlo, Monaco, with more than 100 participating investigators from 16 countries including the undersigned.

Fig. 1 The first 2 publications on the inhalation of insulin in Klinische Wochenschrift in 1924 and 1925.

References

• 1 Bott S, Heinemann L, Rave K, Willavize S A, Carroll R S, Gruber S, Lee J D, Heise T. Time-action profile of an inhaled insulin preparation in comparison to insulin lispro and regular insulin.  Diabetologia. 2000;  43 (Suppl 1) A 46
• 2 Cefalu W T, Skyler J S, Kourides I A, Landschulz W H, Balagdas C C, Cheng S-L, Gelfand R A. Inhaled human insulin treatment in patients with type 2 diabetes mellitus.  Ann Intern Med. 2001;  134 203-207
• 3 Gänsslen M. Über Inhalation von Insulin.  Klin Wochenschr. 1925;  4 71
• 4 Heubner W, de Jongh S E, Laquer E. Über Inhalation von Insulin.  Klin Wochenschr. 1924;  3 2342-2343
• 5 Mudaliar S, Henry R R, Fryburg D A, Becker R HA, Willavize S A, Fisher J M, Fountaine R, Sha S. Within-subject variability of inhaled insulin (Exubera®) versus subcutaneous regular insulin in elderly obese patients with type 2 diabetes mellitus.  Diabetologia. 2003;  46 (Suppl 2) A 277-A 278
• 6 Skyler S A, Cefalu W T, Kourides I A, Landschulz W H, Balagdas C C, Cheng S-L, Gelfand R A. for The Inhaled Insulin Phase II Study Group . Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomized proof-of-concept study.  Lancet. 2001;  357 331-335
• 7 Testa M A, Turner R R, Hayes J F, Scranton R E, Simonson D C. Satisfaction and quality of life with sulfonylurea plus either Metformin or Exubera®: an international randomized Phase 3 Trial. 64th ADA Congress. Orlando; 2004: Abstract Number 487-P
• 8 Testa M A, Hayes J F, Turner R R, Simonson D C. Quality of life improvements in type 2 Diabete when Exubera® is added after failure on metformin monotherapy: an international randomized phase 3 trial. 64th ADA Congress. Orlando; 2004: Abstract Number 1831-P
• 9 Weiss S R, Cheng S-L, Kourides I A, Gelfand R A, Landschulz W H. for the Inhaled Insulin Phase II Study Group . Inhaled insulin provides improved glycemia control in patients with type 2 diabetes mellitus inadequately controlled with oral agents. A randomized controlled trial.  Arch Intern Med. 2003;  163 2277-2282