INHALED INSULIN

by Peter J. Nebergall, PhD

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, as 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 became to moderate the response of the inhaled insulin, to make the dosage "reproducible," so that adjustment of dose could be possible. This has been accomplished. Not unlike "timed-release" oral medications, "inhaled insulins" are encapsulated in soluble "micro capsules," to slow their rate of release. The nature of the human lung dictates rigid size requirements for such "micro capsules," and the problem has been to reliably achieve these sizes.

Several firms have been working to perfect this "micro encapsulation" technology. Both Andaris (from Nottingham, England) and Inhale Therapeutics (from California) have succeeded in micro encapsulating insulin. Andaris states: "Preclinical testing is currently underway."

Inhale Therapeutics, working with pharmaceutical giant Pfizer, has just completed Phase 2 clinicals. Seventy subjects with type 1 diabetes and 51 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 58th 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.

Questions:

Is inhaled insulin available now? No. Phase 3 clinicals are scheduled to start in November. Estimates are 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...