Chapter
14: Oral Hypoglycemic Agents /
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We'd then have
you check your blood sugars before lunch. If your
blood sugar was lower but still elevated, after a
few days, we'd gradually increase the dosage by half
a pill (if metformin) until we got your prelunch blood
sugars into your target range. To do this, we could
go as high as five 500 mg metformin tablets. (Metformin
ceases having any cumulative effect after 2,500 mg.)
If you were to experience gastrointestinal discomfort
at any dose, we'd revert back to the prior dose for
three or four weeks and then increase it more slowly.
Once we determined what
dose of metformin got your blood sugar normalized,
we'd start to shift the dose to before breakfast—immediately
upon arising. In shifting doses, we'd again work in
small increments. Let's say we had found that it took
three 500 mg tablets to get your blood sugars to within
your target range. You'd shift the dose by starting
to take half a tablet immediately upon arising, and
the other 2H tablets immediately after eating. After
a week, provided you didn't experience any intestinal
distress, we'd shift another half a pill to immediately
upon arising, and so on until you were taking all
3 when you got up.
If, after moving a portion
of your dose—say, 1 1/2 tablets—you started experiencing
gastrointestinal distress, we'd shift half a tablet
back to after breakfast. Some people can take several
weeks to acclimate to metformin, so we'd let the regimen
stand for a few days before we'd try moving it again.
We've done this with numerous patients, and it works
for most (though not all) without any undue discomfort.
This cautious tapering up of dose is not necessary
for troglitazone, which is unlikely to cause gastrointestinal
side effects.
This is how we'd get your
postbreakfast blood sugar elevation under control.
Let's look at some other instances where these drugs
can be useful.
Let's say you wake up in
the morning with a higher blood sugar than when you
went to sleep—not an especially elevated blood sugar,
just higher than when you went to bed. This would
tell me that you need some kind of help overnight.
I have many patients whose blood sugars don't go up
after meals but do go up overnight. The cause of the
rise in blood sugars may be slow digestion of dinner
while you're asleep, or may be due to the dawn phenomenon.
Whatever the case, you'd still need something to help.
Here we'd have you take metformin or troglitazone
at bedtime. I'd prefer the troglitazone because it
appears to be longer-acting. Again, it takes 2 hours
for metformin to start working, 30 minutes for troglitazone,
but both drugs appear to work for most of the night.
There's a good chance that
your stomach will be empty at bedtime, so you stand
a higher risk of developing gastrointestinal distress
from metformin. As before, we'd start you with a low
dose and bring it up slowly if you showed gastrointestinal
distress, or rapidly if you didn't. Over time, as
we discovered the proper dose, your blood sugar profiles
would, we hope, show that your fasting blood sugar
in the morning was the same as at bedtime because
of the metformin or troglitazone.
Another instance when we'd
start you on these drugs would be if you showed an
elevated blood sugar at bedtime. This would reflect
the effects of dinner, and to get that under control,
we'd want you on one of them before dinner. Again,
with metformin, we'd start you out on the smallest
possible dose immediately after dinner and eventually
shift the dose to precede the meal. If you were also
showing overnight blood sugar rises, we'd first work
on the dinner dose. Of course, the same protocol can
be applied to lunch if blood sugars are routinely
elevated before dinner. Many of my patients take metformin
before each meal and at bedtime.
Certainly if metformin
were to cause gastrointestinal distress, we now have
the option of switching to troglitazone. It is very
possible that for some individuals we'd use both medications
— perhaps metformin before meals and troglitazone
at bedtime, or vice versa.
Will These Medications
Cause Hypoglycemia?
Some OHAs—specifically
the sulfonylureas—carry the very real possibility
of causing dangerously low blood sugars, but this
is only remotely likely with troglitazone or metformin.
This is because their mode of action is to increase
your sensitivity to insulin. Neither agent interferes
with the self-regulating system of a pancreas that
can still make its own insulin. If your blood sugar
drops too low, your body will just stop making insulin
automatically. Sulfonylureas, on the other hand, because
they stimulate insulin production whether the body
needs it or not, can cause hypoglycemia.
Although the manufacturer
and the scientific literature claim that metformin
does not cause hypoglycemia, I did have a single patient
who experienced hypoglycemia. She was very obese but
only very mildly diabetic, and I was giving her metformin
to reduce insulin resistance and facilitate weight
loss. When I put her on metformin, her blood sugars
went too low—down into the 60s. While it's possible
for any drug to have nearly any effect on a given
individual, this was the only case I've seen of hypoglycemia
with metformin, and I was using it in a patient who
was only mildly diabetic. Her insulin resistance was
causing her to make a lot of insulin, but why the
metformin brought her down so low I can't explain.
So there may be some very
slight risk of hypoglycemia with troglitazone or metformin,
but this is not at all comparable to the great risk
with the sulfonylureas. One warning, however. The
body cannot turn off injected insulin, so if you are
taking insulin plus either of these agents, hypoglycemia
is possible.
What If These Agents Don't
Bring Blood Sugars into Line?
If neither of
these drugs is adequate to normalize blood sugars
completely, chances are there is something awry in
the diet or exercise portion of your treatment program.
The most likely culprit for continued elevated blood
sugars is that the carbohydrate portion of your diet
is somehow not properly controlled. So the first step
is to examine your diet again to see if that's where
the problem lies. With many patients, this is a matter
of carbohydrate craving, patients eating restricted
foods. If this is the case, if your carbohydrate craving
is so overwhelming, I'd recommend that you look at
appetite-suppressing medication as a way of getting
uncontrollable craving into line. If diet is not the
culprit, then the next thing—no matter how obese or
resistant to exercise you might be—would be to try
to get you started on a strenuous exercise program.
If even this doesn't do the trick, we'll certainly
use injected insulin. Another far-out possibility
(I say far-out because I haven't tried it yet) would
be to use both metformin and troglitazone together.
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