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THE FUTURE OF INSULIN: PILLS, PATCHES, AND PUFFS ARE SLOWLY COMING DOWN THE PIPELINE

by Terri Kordella

There are 17 million people in the United States who have diabetes. More than a fifth of them take at least one insulin injection a day. Insulin injections are often necessary for controlling blood sugars to decrease the risk of complications and improve health. For those with type 1 diabetes, it’s a matter of day-to-day survival. But type of diabetes aside, insulin shots are a fact of life for almost four million Americans.

For now.

Several companies are working on developing new ways of taking insulin, from pills to patches to mouth sprays to inhalers. Recent headlines in the popular press may make it seem like these products will be available soon. But the truth is, as FORECAST went to press, none of these products had been submitted to the Food and Drug Administration (FDA) for approval, and there is no guarantee any of them will pass muster. The ones furthest along in development are probably at least two years away from becoming available, even if the FDA approves them. The exception would be if the FDA decides to "fast-track" any of them. When a product is "fast-tracked," it has priority review, and the FDA may render a decision about approval in as little as six months.

That said, several new forms of insulin delivery do look promising. What could be in store? What might the future of insulin look like?

Insulin Inhalers

More companies are working on insulin inhalers than any other insulin delivery option. Insulin inhalers would work much like asthma inhalers. You would breathe the insulin in through your mouth and it would be absorbed through your lungs. The insulin, either a powder or liquid, would be fast-acting, so you would take it at mealtime.

There are two challenges with insulin inhalers, however: the rate of absorbency and side effects. How much insulin you actually absorb through your lungs may be affected by your age and your respiratory shape. Side effects range from mild cough to more serious, if rare, conditions such as scarring in the lungs.

As Forecast went to press, the front-runner in the race for inhalable insulin appeared to be Exubera, a combined effort of Inhale Therapeutic Systems, Inc.; Pfizer, Inc.; and Aventis Pharma. Phase III trials had been completed, and the companies are undertaking additional long-term studies before determining if and when they will submit Exubera for FDA approval. Once they file, it may take two to two and a half years for the FDA to review the trial data and make a decision, unless Exubera is fast-tracked.

Mouth Sprays

Mouth sprays deliver insulin through an aerosol spray. They differ from inhalers, however, because the insulin would be absorbed through the inside of your cheeks and in the back of your mouth instead of your lungs.

Two forms of mouth spray are in development, one that is fast-acting and one that would cover the basal rate of insulin. (The basal rate is the amount of insulin you need throughout the day to keep blood sugars stable.) Generex Biotechnology is developing these sprays in Canada, and is partnering with Eli Lilly and Company in the United States.

Pills

The biggest challenge with insulin pills to date has been posed by the human digestive system. Either the gastrointestinal tract breaks the insulin down or the insulin passes through the system intact because it is unable to pass through the gastrointestinal membrane. In both situations, the insulin does not make it to the liver and then the bloodstream, which is where it needs to go to reach the muscle cells and do its biochemical duty.

Several manufacturers are working on pills. In these pills, special molecules attached to the insulin would help it reach its destination either by helping to prevent the insulin from being broken down, escorting the insulin through the gastrointestinal lining, or both.

Insulin from pills would reach its peak action about 15 minutes after you swallow them, so pills would be considered fast-acting.

The Patch

Most of the other forms of insulin in development are fast-acting, so your mealtime dose would be covered. But where does that leave you for a basal insulin?

The answer may be an insulin patch in pre-clinical testing at Altea Development Corporation. Using the patch would be a two-step process. First you would use a device that would make microscopic holes in the top layer of your skin. Then you would apply the patch.

Although Altea is working on a 24-hour patch you would only have to apply once a day, the patch is still in the earliest stages of development, so it may turn out to be a 12-hour patch instead.
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Terri Kordella is associate editor of Diabetes Forecast.
Copyright © 2003 American Diabetes Association
From DIABETES FORECAST, March 2003
Reprinted with permission from The American Diabetes Association.