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.