Alternative Insulin Delivery Systems: |
Ever since insulin was first identified
as the key to restoring normal glucose
levels in people with diabetes, doctors and
patients have been hoping for an alternative
to insulin injections. Don't get us wrong,
injecting insulin works pretty well. Many
people have been able to lead relatively
normal lives because of it. The new
technology has pretty advanced syringe and
needle technology and insulin pens and pumps
have made getting insulin into the body even
easier. Even so, the quest continues to find
an alternative way of administering insulin.
Scientists have been working on a number of
new advances in insulin administration.
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Transdermal (through the skin): |
 Our
skin is a remarkable organ. It's very good
at letting almost nothing in, and letting
just a few selected things out. Patches to
help people quit smoking have made it seem
almost easy to deliver a drug through the
skin. In fact, nicotine is a small molecule
that is readily absorbed into the skin. It
only takes a tiny amount to have an effect
on the body. Insulin on the other hand, is
far too large to get through the skin
without a lot of help. Trying to change that
is tough.
Scientists have been working on patches
using electrical currents, ultrasound waves,
and chemicals to help transport insulin
through the skin. Although some companies
are hoping to develop products that could
provide boluses of insulin through the skin
for mealtime, any success for transdermal
delivery is likely to come with basal
delivery of relatively small amounts over
time. Either way, we have a while to wait
before insulin patches might be available in
pharmacies.
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| Buccal: |
 Buccal
insulin is similar to inhaled insulin in
some ways. Buccal or delivery into the
mouth, involves a device that delivers a
spray of insulin like what you'd get out of
a can of spray paint. Instead of going into
the lungs, the insulin is absorbed in the
lining at the back of the mouth and throat.
The good part is that it avoids any problems
from putting large amounts of insulin in the
lungs. The problem is that even more of the
insulin gets wasted.
Other than that, research shows that buccal
insulin works about as well as inhaled
insulin.
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| Oral: |
 You
probably already know that insulin taken as
a pill is quickly broken down in the
stomach, just like the food you eat. That
makes it useless for lowering blood glucose
levels.
So insulin can't be taken by itself in a
pill form. Some scientists are trying to
"package" insulin using special coatings, or
by altering the insulin structure to get it
through the stomach. Like inhaled insulin
and insulin sprays, it's likely that a lot
of the insulin will be wasted before it gets
where it's going. It would probably also
take a long time to start working after you
swallowed the pill. Not much research has
been done on insulin pills so far.
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Inhaled insulin: |
 For
over 80 years exogenous insulin has been
given by injection. The injection devices
have improved-disposable syringes and pen
injection devices are more convenient and
less traumatic than the boil to sterilize,
use until too blunt devices of
yesteryear-but patients and healthcare
professionals remain uneasy about the
concept of injections.
Yet the evidence based drive for
increasingly tight glycemic control means
that more patients should be offered more
injections Inhaled insulin is probably what
you've been hearing the most about lately.
Several products are being created in
laboratories and have shown success at
controlling blood glucose levels. Some of
these are in phase 3 clinical trials (the
final phase of testing before you can submit
a device for FDA approval), but only one has
been approved for use. And that one is only
approved for adults.
In clinical trials, the inhaled insulin,
managed blood glucose levels as well as
injected fast-acting insulin. Inhaled
insulin does not replace longer-acting
insulin, so those would still need to be
injected.
Insulin can be effective given by
inhalation. This was first shown in 1971,
although the early work was not pursued, and
it was not until 2000 that the modern era of
inhaled insulin began. The bioavailability
is 10-15% and the dose equivalent about
three times that of injected insulin.
The pharmacodynamic of inhaled insulin offer
an action profile with a fast onset
(although slightly longer run-off) closely
related to that of rapid acting insulin
analogues given subcutaneously, which in
studies have shown better postprandial
glucose control and less tendency to
nocturnal hypoglycemia.
In patients with type 2 diabetes, adding
inhaled insulin to oral hypoglycemic
regimens does improve control more than
doing nothing. This is important-apart from
patients' comfort-an expensive new insulin
could have huge potential advantage if it
encouraged adherence and resulted in more
patients with diabetes achieving treatment
targets. Sadly, the published data on
patients' satisfaction, superficially
encouraging, are difficult to interpret, as
invariably patients have been comparing a
new treatment with an old one. When a
specially designed questionnaire was used,
treatment satisfaction improved
significantly in patients with type 1 and
type 2 diabetes on taking part in the
trials, irrespective of whether the mealtime
insulin they took were injected or inhaled.
Although the improvement was greater with
inhaled insulin, the injected insulin
treatment was identical to pre-trial
treatment limiting the potential for
improvement. Notably, improvement in
treatment satisfaction correlated with
improved glycemic control.
Might greater satisfaction have been
obtained with injected regimens if these had
been optimized effectively? Were the studies
just too short to show the biomedical gains
one might anticipate from a treatment
expressly designed to support compliance, or
do the problems of insulin therapy extend
beyond a dislike of needles?
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Inhaled insulin has potential problems: |
The new inhaled insulin does not come
without limitations:
►Patient have to inhale a lot of insulin to
get the amount your body needs. This is
because only a small percentage of the
inhaled insulin actually reaches the
bloodstream and lowers blood glucose. So, a
lot of it is "wasted." Because of that, the
cost of inhaled insulin is fairly high - the
waste must be paid for.
►There are also questions about the safety
of delivering insulin to the lungs. After
all, that's what you're doing when you
inhale the insulin.You send it straight to
the lungs. Many scientists think the lungs
are a great place to deliver a drug because
of the large surface area and ready
absorption. There have been concerns about
possible long term effects of insulin on
lung structure and function, although
current published trials report no
deleterious effects over the short-term. The
fact remains:" that is not what lungs were
designed to do".
►Although inhaling insulin has proven safe
in short-term studies, the long-term safety
remains a question.
►The bioavailability is affected by asthma
(decreased) and smoking (increased). If
patients really dislike injections so much
inhaled insulin might make its biggest
impact on complications of diabetes if it
were to be available only to proved
non-smokers.
►Formation of anti-insulin antibodies is
higher with inhaled insulin, and although
this is dismissed as not affecting insulin
requirement over time, older diabetologists
will remember the drive to reduce insulin
antibody formation, with the fears that
antibodies delay and render unpredictable
insulin absorption and even that
antibody-antigen complexes may increase risk
of micro-vascular disease.
Few people like injections and some are so
terrified they refuse appropriate treatment
for diabetes. Many are discouraged by
previous experience of injections-none of
whom will have used current insulin
injection devices-and by healthcare
professionals using injection therapy as a
threat in a (vain) attempt to improve
adherence.
For patients with established type 1
diabetes lack of freedom to eat or not eat
and the demand for (painful) blood glucose
testing may be much more of an issue than
injection therapy itself.
In one study only 14% of injections were
missed because they were injections. In this
group healthcare providers will need more
robust evidence of patients' preference than
is currently available. Where inhaled
insulin could really have an impact (in the
developed world) will be if healthcare
professionals and patients start to use
insulin much earlier and more aggressively
in type 2 diabetes, affecting the
progression of diabetic complications.
Meanwhile, all patients are waiting to see
if the new inhalations are safe. If they
are, and if they are cheap enough, at least
one barricade to better diabetes treatment
may fall.
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Is Inhaled Insulin as Good as Insulin
Injection? |
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Because people with type 1 diabetes can't
make insulin and need to take it, they
usually need more than one type of
manufactured insulin to control their
diabetes.
The different types of insulin work at
different rates and for different amounts of
time. Three commonly used types of
insulin are "short-acting,"
"intermediate-acting," and "long-acting."
A-"Short-acting" insulin works much
faster than intermediate- or long-acting
insulin, and it is used around mealtime.
Short-acting insulin should be taken about
30-45 minutes before eating, and it peaks at
about 2-3 hours. It can keep working for as
long as 6 hours.
B-"Intermediate-acting" insulin is
insulin mixed with a substance that makes
the body absorb the insulin more slowly. It
takes longer to start to work, and it stays
in your body for a longer time. NPH is a
type of intermediate-acting insulin that
usually begins to work about 2-4 hours after
injected. It peaks 4-10 hours after
injection, and it keeps working for 10-16
hours.
C-"Long-acting" insulin starts to
work in 6-10 hours and can stay in the body
for 20 hours or more. It has a peak, but its
top speed looks a lot like its normal speed.
Like intermediate-acting insulin, it is
usually taken in the morning or before bed.
People with type 1 diabetes can often keep
their glucose levels under control by taking
shots of intermediate-acting or long-acting
insulin in the morning or before bed, as
well as taking shots of short-acting insulin
before meals. However, even though this type
of routine has been shown to work for people
with type 1 diabetes, many patients often
stray from this routine, probably because of
the burden of taking so many shots. |
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