June 18, 2002 -- Diabetes patients tired of needles may soon be able to get their insulin through pills, patches, mouth sprays, or inhalers.
"I see patients every day struggling to manage their diabetes," says American Diabetes Association (ADA) president Christopher D. Saudek, MD, a professor of medicine at Johns Hopkins University in Baltimore. "Insulin without injections has been dreamed of since the invention of insulin."
Ideally, doctors would like to grow new insulin-producing cells to replace the missing or damaged cells that can cause diabetes, Saudek says. At this year's annual meeting, the ADA board of directors voted to support legislation allowing human cells to be cloned for use in such treatments.
But it will be a long time before this technology is available. In the meantime, researchers have developed several promising methods for taking insulin with less pain.
Imagine the ease of swallowing an insulin pill. If it works, diabetes patients would not only avoid needle pricks, but they'd get a higher proportion of insulin to the liver -- which plays a key role in processing the hormone -- than they do with injections. That's important, because in order to get a sufficient amount of insulin to the liver, people taking insulin by injection often get too much of it in other parts of their bodies, putting them at greater risk of side effects such as heart disease.
Until recently, though, no one could figure out how to get insulin through the wall of the patient's gut. What insulin a patient swallowed would pass uselessly out again.
But that's changed. Several researchers have developed an insulin pill that, in early studies, appears to work.
Scientists from Emisphere Technologies of Tarrytown, N.Y., say they have developed chemicals that can temporarily change the shape of an insulin molecule so it passes through the wall of the gut into the bloodstream.
An initial study in 12 nondiabetic people found that the Emisphere capsule did increase their insulin levels and lower their blood sugar without causing side effects. The company plans to proceed with studies in diabetes patients.
Another oral drug -- Hexyl-Insulin Monoconjugate (HIM2), developed by Nobex and GlaxoSmithKline -- offers similar advantages.
But there's a drawback. The human body needs insulin at all times, but the amount needed goes up sharply at meal times because insulin helps the body metabolize sugar. The pills provide a quicker rush of insulin than injections do, but can't deliver the small, steady doses needed between meals.
The insulin pill may be of use to people with milder diabetes, whose bodies produce some insulin. But those who don't produce enough of their own insulin would still have to turn to needles a couple of times a day to maintain the levels needed between meals.
Also, the pills still require a person to take large amounts of insulin because much is still lost before making it to the bloodstream.
Several companies -- 10 of them presented work at the ADA meeting -- are developing insulin inhalers similar to those used to treat asthma.
"The first paper on inhaled insulin was published in 1925," said Jay S. Skyler, MD, a professor of medicine, pediatrics, and psychology at the University of Miami in Florida. "But there was not much progress until recently."
Scientists had been challenged to create a form of insulin that allows a person to puff sufficient drug into the lungs to be effective. Now, it appears they've overcome these obstacles and preliminary studies look promising, said Skyler. "I fundamentally decided that this does represent a viable alternative. Some type 2 patients could avoid injections altogether."
Few side effects were reported, though one laboratory study suggested a risk that inhaled insulin could cause harmful constriction of blood vessels in the lungs. "The long-term safety still has to be established, but the progress is quite good," said Skyler.
Results were similar in studies on Oralin, an aerosol spray being developed by Generex Biotechnology. The spray is similar to the inhalers but is absorbed through the lining of the mouth and throat instead of the lungs.
The drawbacks of the inhalers and sprays are similar to those of the pills: they can't yet be used to supply insulin between meals, and a lot more insulin must be given to achieve the same level in the blood as the person would get from an injection.
Researchers are developing an interesting fourth alternative that might complement any of the other three: an insulin patch.
Patches designed by Altea Development transmit insulin through the skin in the low, steady quantities needed between meals.
The patch works in a two-stage process: First, a reusable electronic patch powered by a small battery painlessly burns microscopic holes in the outer layer of skin. Next, a patch containing insulin is applied in much the same way as the nicotine patch used by people who are trying to quit smoking.
So far, the patch lasts for 12 hours. Altea is developing versions that might last for several days, as well as one that might deliver the high, short-term dose of insulin needed at meal times.
All the new methods -- inhalers, sprays, patches, and pills -- must undergo much more testing before they become available.