Experts say oral insulin product shows promise

Initial studies show it’s as effective as injections

The days of multiple needlesticks could be numbered, say researchers working with a new oral insulin product that appears to be as effective as injected insulin.

The small rapid-mist-dispensed insulin, under development by Generex Biotechnology Corp. of Toronto, is "the first and only oral insulin that can be absorbed through the mouth," says Arthur Krosnick, MD, a diabetologist and clinical associate professor at Robert Woods Johnson Medical School in Princeton, NJ. "Every patient involved in the trials says he will take it anytime instead of insulin," he says.

Taking it anytime is not quite in the cards — at least not yet. The product, which will be sold under the name Oralgen in the United States, is intended for pre-prandial use, although the company’s researchers are working on a long-acting product to be delivered the same way, Krosnick explains. The short-acting oral product is now at the end of Phase II clinical trials and is expected to begin Phase III trials soon. Patients will still have to inject long-acting insulin once or twice daily.

Studies in Texas, California, and Canada show insulin levels begin to rise within 10 minutes of taking the medication and peak in 30 minutes to one hour, then slowly dissipate over two to three hours, mimicking the normal insulin function. While blood sugar levels drop after the insulin dissipates, the medication does not produce hypoglycemia, he says.

Studies also have shown it is equally effective in producing glycemic control in patients with Type 1 and Type 2 diabetes.

The oral medication is dispensed through a device that looks like an asthma inhaler, but the product does not go into the lungs, and it is not swallowed. Instead, a fine mist comes in contact with the mucous membranes of the mouth. The patient holds it in for a few seconds. "The only unpleasantness associated with it is a slight medicinal taste for about three seconds," says Krosnick.

Patients are more than willing to put up with that minor discomfort, he says. "Needlesticks are hurtful. [Patients] tell me this is a godsend because they only have to inject in the morning and evening now and can use the oral insulin at mealtimes."

"We have to make it easier for patients to live with diabetes," Krosnick says. For 1.5 million patients with Type 1 diabetes and approximately 4 million with Type 2 diabetes who need insulin, not only will quality of life improve, but compliance will likely improve as well since self-management will be less painful, he predicts.

The potential of the new product has generated excitement in the medical community. "It looks impressive," says William Duckworth, MD, director of diabetes research at the Veteran’s Affairs Medical Center in Phoenix and professor of microbiology and cellular biochemistry at University of Arizona, also in Phoenix.

Duckworth, who has not been involved in any clinical trials of the oral insulin, says absorption of insulin through the oral mucosa would likely be faster than subcutaneously injected insulin. "That is what is most attractive about it. A patient could take it with a meal or even after a meal and get rapid absorption rather than depend on the sometimes erratic absorption of any subcutaneously delivered insulin." He speculated that the new product could be "more consistent even than Humalog."

"It’s a race between inhaled or oral insulin, and certainly oral insulin is a far better way to go than through pills," Duckworth says.

At least two companies are investigating the effectiveness of inhaled insulin, which generated a great deal of excitement a couple of years ago. The medication is delivered as a fine powder, inhaled in measured doses through a device similar to an asthma inhaler.

While Phase III trials were set to begin on at least one of those products last year, some questions from the U.S. Food and Drug Administration are still being addressed, says Duckworth, who has worked on those trials.

[Contact Arthur Krosnick at (609) 683-4655 and William Duckworth at (602) 277-6436.]