Insulin Without Injections

  June 17, 2002

  By Lisa Ellis
  InteliHealth News Service

  SAN FRANCISCO Ever since researchers figured out 80 years ago how to
  treat diabetes with insulin, they have been trying to find a way to avoid using
  needles and injections to deliver the drug.

  New research presented at a conference here suggests that the realization of
  that dream may be moving closer.

  Several types of insulin inhalers are working well in clinical trials, although
  questions remain about long-term safety and cost effectiveness. And the
  newest research indicates that it also might be possible to deliver insulin
  through a patch, a mouth spray or even the long-elusive goal ?a pill.

  Several studies on new ways to deliver insulin were presented during the
  American Diabetes Association's annual scientific sessions here.

  Except for inhalers, which have been in development for several years, all of
  the new methods are in very early stages of human testing and are not likely
  to come to market any time soon.

  Implantable pumps already are available to deliver a steady dose of insulin
  for people whose bodies do not produce it, a condition known as type 1
  diabetes. The patch also is designed for this purpose, but it is so new that it
  has been tested only for safety, not effectiveness.

  All of the other methods are designed to deliver a burst of fast-acting insulin
  before meals. These insulin booster shots are needed by both type 1
  diabetics and by type 2 diabetics who cannot adequately control their blood
  sugar with medicines.

  The bodies of type 2 diabetics make insulin, but their bodies do not use it
  efficiently to help the body turn blood glucose (sugar) into energy. This leads
  to high levels of blood sugar, which can cause dangerous short-term and
  long-term problems.

  In a news conference and in conference sessions, researchers described the
  progress and the concerns of research so far on these alternative ways to
  deliver insulin.

  Pills

  Two products now under investigation may have solved the long-knotty
  dilemma of how to get insulin into the system by swallowing it, researchers
  said. This has not worked in the past for two reasons: The insulin molecules
  do not pass through the intestinal wall, and insulin is broken down by
  digestive enzymes.

  Researchers for Emisphere Technology and Nobex Corp. say they have
  solved this problem, using two different methods.

  Emisphere Most insulin molecules are shaped in a way that cannot
  penetrate the intestinal wall, but a few of the molecules are more slender and
  can pass through, said Michael Goldberg, M.D., chairman and CEO of
  Emisphere. He said his company's insulin pill works by attaching the delivery
  agent to the slender molecules, which pass through the intestinal wall and
  into the liver, then the bloodstream.

  The Emisphere pill, still unnamed, has been tested only in very small studies
  involving about 30 patients. According to results reported at this meeting, the
  insulin entered the bloodstream, reaching peak levels within 25 minutes.

  HIM2 This pill, being developed by Nobex in association with
  GlaxoSmithKline, uses a form of polymer to prevent the insulin from being
  broken down in the intestines. The insulin then moves into the liver and has
  its primary effect there, as with the Emisphere pill.

  Stephen Clement, M.D., an associate professor of medicine at Georgetown
  University and consultant to Nobex, said the liver is signaled by the body's
  natural insulin to make glycogen, a storable form of sugar that can be
  converted to useable sugar when needed. Converting the liver's sugar supply
  to its properly stored form by delivering supplemental insulin to the liver
  might help to prevent the wide fluctuations of blood sugar diabetics can get
  with injected insulin, Dr. Clement and Dr. Goldberg said.

  HIM2 was tested in six patients, who took HIM2 before a meal. The insulin
  reached its peak in the bloodstream after about 15 minutes, Dr. Clement
  said. Then 31 patients with type 1 diabetes were given either HIM2 or
  injected insulin. Blood sugar levels were about the same between the two
  groups, he said.

  Inhalers

  Five different products are under development now, and all are at least
  several years away from U.S. government approval and marketing.

  Nevertheless, inhaled insulin has been shown in numerous clinical trials of
  various products to deliver insulin quickly into the bloodstream, said Jay S.
  Skyler, M.D., in a symposium on inhalers. It may be "the first realistic way"
  to replace before-meal insulin injections, said Dr. Skyler, a professor of
  medicine, pediatrics and psychology at the University of Miami and past
  president of the American Diabetes Association.

  Inhalers convert insulin in a liquid or dry powder form to a breathable
  medicine that is inhaled into the lungs and passes from there into the
  bloodstream. The various products have different designs and different
  advantages and disadvantages.

  There are a few potential problems, Dr. Skyler and others noted:

       With most inhalers, the body is able to use only 10 percent to 16
       percent of the insulin because the rest is exhaled or swallowed rather
       than getting into the lungs.
       This could make inhalers more costly than injected insulin.
       There is some concern about the long-term effects of an inhaler on
       people with respiratory problems. Results so far are mixed.

  Patch

  This product, being developed by Altea Development Corp., is intended to
  replace the "basal" insulin that keeps the system of type 1 diabetics stable
  throughout the day and night. This now is delivered through injections or a
  pump.

  The patch uses a battery-powered device to make microscopic pores in the
  skin, said Alan Smith, Ph.D., vice president of research. Then this device is
  removed and the insulin-containing patch is applied, he said.

  Tests on a small number of healthy volunteers shows that the insulin is
  absorbed by the body gradually and that the tiny pores disappear as the
  body replaces dead skin cells, he said. No tests have been done yet to see if
  the patch is effective for diabetic patients.

  Oral spray

  This spray puts insulin into the bloodstream through the inside of the cheeks,
  said Pankaj Modi, Ph.D., vice president of research and development at
  Generex Biotechnology Corp. Generex is developing the liquid aerosol spray,
  called Oralin.

  Modi said the spray was tested in 750 patients with type 1 and type 2
  diabetes in three- to six-month studies. He said the spray worked about as
  well as injected insulin among these patients, and reached its peak in the
  bloodstream faster.

  Chris Saudek, M.D., president of the American Diabetes Association,
  cautioned that patients who take insulin by injection should not think they'll
  be able to give up injections any time soon.

  "Each of these approaches is at a different stage of development," said Dr.
  Saudek, a professor of medicine at Johns Hopkins University. "Obviously, the
  earlier in the development phase, the higher the risk that it will never come
  out" for public use.

  Most people with diabetes can learn to use insulin well and without pain, said
  Dr. Saudek, who has been involved in the development of insulin pumps. But
  these new techniques also have the potential to help prevent some
  fluctuations of blood sugar that often occur with injections, he said.