Oral Diabetes Medications

Oral Diabetes Medications

REVIEW OF ORAL DIABETES MEDICATIONS
by Peter J. Nebergall, PhD

Currently there are an estimated 16 million

diabetics in the United States. Perhaps 10 percent are

insulin-dependent; the rest are type II diabetics, controlling

their condition with diet, exercise, and oral medications.

Oral medications are not insulin pills, rather

four classes of drugs designed to improve the body's utilization

of what insulin is still present. These are: The sulfonylureas,

metformin, troglitazone, and acarbose.

Most "diabetes pills" are

sulfonylureas, a class of chemicals that stimulate the pancreas

to produce more insulin, effectively lowering blood glucose

levels. Type II diabetics, those who need better management than

diet and exercise can provide, often turn to these medications:

tolbutamide, chlorpropamide, tolazamide, glyburide, glipizide,

and new glimepiride for effective self-management. The

sulfonylureas are effective, but only so long as the pancreas

maintains some of its insulin-making capacity.

But the sulfonylureas grow ever less effective

with the passage of time. They drive the failing pancreas to

greater effort, but the patient may well require ever-increasing

doses. At some point, no further increase in medication will be

effective; the pancreas isn't doing its job, and the patient

needs to start injecting insulin. When the islet cells of the

pancreas stop making sufficient insulin, insulin must be

injected.

Metformin, the second of the oral diabetes

medications, works to raise the body's sensitivity to its own

insulin. Used for decades in Europe, it can be prescribed alone

or with the sulfonylureas. Metformin helps the type II diabetic

make better use of the insulin he or she has left. Like the

sulfonylureas, it becomes useless when the pancreas ceases

producing adequate insulin.

Troglitazone (trade name Rezulin, from

Parke-Davis) is the third oral medication. Rezulin directly

attacks the problem of insulin resistance, the increasing

inability to process insulin, that is the chief component of type

II diabetes. In tests, Rezulin enabled many diabetics to reduce

volume and frequency of insulin injections. A few were able to

discontinue insulin injections entirely.

Initially, Rezulin was tested and approved for

use with insulin-using type II diabetics. As tests continued, it

became clear that it was also an effective blood glucose reducer

either alone (in combination with diet and exercise) or in

combination with a sulfonylurea, for type II diabetics who did

not need insulin (although not a replacement for the

sulfonylureas). On August 4, 1997, the Food and Drug

Administration approved Rezulin for these new uses.

As with other oral diabetes medications,

Rezulin's effectiveness depends on the presence of insulin. If

sufficient insulin is not present, it must be injected, and

Rezulin therapy will not change that fact. Where insulin supply

rather than insulin resistance is the issue (as in type I

diabetes), Rezulin therapy offers nothing. Investigations

continue, and new uses may come with time. "Because of its

mechanism of action," states Parke-Davis, "Rezulin is

active only in the presence of insulin. Therefore, Rezulin should

not be used in type I diabetes or for the treatment of diabetic

ketoacidosis."

Published data state that although degree of

renal insufficiency has no effect on Rezulin dosage, persons with

hepatic (liver) disease should exercise caution. Other data warn

that in premenopausal anovulatory women, Rezulin therapy may

result in resumption of ovulation, and risk of pregnancy. There

is further recommendation to proceed with caution if the

individual is taking antirejection drugs such as cyclosporine or

tacrolimus.

Acarbose, the fourth of the current "oral

meds" is completely different. A carbohydrase inhibitor, it

temporarily suppresses the digestive enzymes which turn

carbohydrate into glucose, slowing digestion and glucose

absorption, keeping glucose levels more even. More a management

tool than an antidote to insulin shortage, acarbose helps some

diabetics keep a more constant blood glucose level. A

"temperamental" medication, it has many side effects,

and is less than universal in its utility.

Problems

Unfortunately, oral medications are often

eventually insufficient. Many type II diabetics, diagnosed as

young adults, at first successfully control their condition with

diet and exercise, but find they need the pills as they grow

older. A number of years (and dosage increases) later, these

diabetics have reached the limit of what oral medications can do

for them; they are "maxed out," and really need to

start injecting insulin. (Note: Regular, frequent blood glucose

monitoring will show if you have reached the point where you

should begin insulin therapy.)

Here we encounter what the drug companies call

"psychological insulin resistance." Some of this is

plain old fear of sticking yourself with needles--nurtured by

memories from our childhood in the bad old days of dull-as-nails

reusable syringes! Many men would rather face a bayonet. But some

doctors contribute to the problem when they don't make it clear

to the patient what the high glucose levels consequent to

remaining on now-useless oral medications will bring in their

wake. Yes, insulin is a powerful medication, with risks if used

incorrectly--but what in this world DOESN'T have risks if used

incorrectly? The risks of remaining on oral diabetes medications

once pancreatic insulin has diminished or ceased entirely are far

greater than the risks of taking insulin.

Oral Insulin?

Recent reports have mentioned insulin

administration by mouth. The nature of insulin, and of human

digestion, make oral administration of insulin ineffective for

blood glucose management--the insulin is digested before it can

reach the bloodstream. The oral insulin administration here noted

is taking place as part of several diabetes prevention trials. In

one example, individuals considered at high risk for developing

diabetes (but not yet "diabetic") are given oral

insulin in an effort to misdirect their body's autoimmune attack

on the Beta cells of the pancreas. Oral insulin, very

"investigational" at this time, is not currently an

option for blood glucose management.

The Future

Researchers at Johns Hopkins are testing

aminoguanidine, a new medication that may prevent or reduce some

of the ramifications of diabetes. Ergo Scientific Company's

Ergoset, currently in Phase III clinicals, appears to reduce the

high plasma lipid levels common in type II diabetes, and thus the

risk of diabetic heart disease. Swedish and American researchers

are testing still another (APO A1 MILANO, covered in VOICE Volume

10, Number 4) that may help reduce diabetic heart disease.

Aerosol spray insulin (for nasal administration) is being tested,

and may someday supplant injection. Trental (pentoxifyline, from

Hoechst Marion Roussel) is now available to treat

"intermittent claudication," a painful circulatory

ailment and frequent companion of peripheral neuropathy. ACE

inhibitors, a class of blood pressure medications like Capoten

(Captopril), have been proven to deter and retard diabetic kidney

complications. Other oral medications are constantly being

evaluated for possible diabetic applications. Change is coming

quickly.