by Peter J. Nebergall, Ph.D.
From the Editor: The following article is reprinted from the Fall, 1998, issue of the Voice of the Diabetic, a publication of the Diabetes Action Network, a division of the National Federation of the Blind. Everyone concerned about effective management of diabetes will be interested in what Dr. Nebergall has to say:
Ever since insulin was first isolated in 1921, folks have dreamed of a more attractive way to take it than by parenteral injection. Who likes needles? Many alternatives to the syringe have been tried, but the successful ones (the insulin pen, the insulin pump, needle-free air injection) still had to penetrate below the skin to inject the dosage. Oral insulin (insulin pills) was tried but found ineffective because the body's gastric juices destroyed the medication long before it could be absorbed into the blood. Early attempts to inhale dry, powdered insulin worked but proved impossible to moderate; administration produced quick absorption followed by rapid fall-off.
The problem was to moderate the response of the inhaled insulin, to make the dosage reproducible, so that adjustment of dose would be possible. This has been accomplished. Not unlike timed-release oral medications, inhaled insulins are encapsulated in soluble microcapsules to slow their rate of release. The nature of the human lung dictates rigid size requirements for such "microcapsules," and the problem has been to achieve these sizes reliably. Several firms have been working to perfect this microencapsulation technology. Both Andaris (from Nottingham, England) and Inhale Therapeutics (from California) have succeeded in microencapsulating insulin.
Andaris states: "Preclinical testing is currently underway." Inhale Therapeutics, working with pharmaceutical giant Pfizer, has just completed phase two clinicals. Seventy subjects with type 1 diabetes and fifty-one with type 2 were randomized into inhaled or conventional treatment regimes. A related study of the reproducibility of inhaled dosage (through an inhaler device developed by Inhale Therapeutics) was completely successful. "Inhaled insulin administration was consistent from dose to dose, even with inexperienced users...pulmonary dosing is as consistent as injection."The results of these two three-month trials were made public at the American Diabetes Association's fifty-eighth annual scientific sessions in Chicago, Illinois, June 16, 1998. Researchers reported that, when inhaled insulin was used as a replacement for quick-acting, mealtime-injected insulin (with longer-acting basal insulin still injected), the degree of control was approximately equal, with the added benefit of increased patient compliance.
* Is inhaled insulin available now? No. Phase 3 clinicals are scheduled to start in November. Estimates are that the new insulin may be on the market in three to five years.
* Is it a total substitute for injected insulin? No, current inhalable formulations are designed to cover mealtime needs; basal insulin would still be injected. This may well change.
* Is it tight control? Not yet. At this time researchers compare it favorably to one injection of long-acting insulin taken in the morning. Expect this to improve.
* Is this the wave of the future? Very possibly. Both Inhale Therapeutics and Andaris report progress on a dozen or more different inhalable medications. With luck we may not need the syringe too much longer.