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Diplomate, American Board of Internal Medicine and Diabetes Specialist Oral agents for diabetes have become available in the United States. These
agents work by stimulating the pancreas (the organ that makes insulin) to release
more insulin into the blood stream. Now, with better understanding of the
pathophysiology (cause) of this disease, we have no less than three different
classes of drugs for diabetes, and they all work outside of the pancreas.
The two types of diabetes are called "Type 1" and "Type 2". Type 1 diabetes
usually starts at a young age (hence, formerly called Juvenile diabetes), and is
characterized by absence of circulating insulin. Type 1 diabetes can ONLY be
controlled by insulin shots.
Type 2 usually starts in middle age and can usually be controlled with diet
and oral agents. The majority of insulin users today, however, are actually Type 2
diabetics, but the trend is changing.
The majority of Type 2 diabetics have normal or even elevated insulin levels
and the defect lies in their bodies being unable to utilize their own insulin.
Therefore, we have what is called insulin resistance. The action of two new classes
of diabetes drugs is directed towards attacking this insulin resistance.
I like to use the analogy of the insulin resistance of insulin receptors being a
lock that has to be opened by a key, which is insulin, in order for the door to open to
allow the entry of glucose (sugar) into the tissues. If the locks are rusty, they need
to be lubricated to allow them to be unlocked. The two classes of new drugs, which
facilitate utilization of insulin, are called "insulin receptor sensitizers".
One of these classes is called Metformin (brand name Glucophage) and the
other is called Troglitazone (brand name Resulin). Besides acting on the insulin
receptors, these drugs also have an effect on the liver, which stores 75-80% of the
body’s stored sugar, called Glycogen. Normally, the liver releases adequate
amounts of Glycogen to supply vital organs like the brain, heart, and kidneys, which
need sugar to maintain their function. Metformin and Troglitazone can regulate the
release of this stored sugar thus improving diabetes control.
If you are a couch potato or refuse to exercise, blood sugar can go up as a
result of poor utilization of sugar in periphery or muscle tissues. Troglitazone helps
to improve utilization of insulin in muscle tissues and Metformin may also have
some effect on the peripheral receptors in the muscle. These drugs can work alone
and in combination with other agents. I have been successful in switching Type 2
diabetic patients from insulin to one of these agents, usually in combination with a
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sulfonylurea agent. This process should only be undertaken under the guidance of
your primary care physician or a diabetes specialist. Metformin can cause
dangerous side effects in patients with certain other conditions. Troglitazone has
fewer side effects, but is considerably more expensive.
The third new class of drug is called Acarbose (brand name Precose). The
main action of this agent, in the digestive tract, is to block absorption or more
complex sugars or carbohydrates and is especially good for lowering blood sugar
after a meal.
These new drugs can also be used in combination with Sulfonylurea and
insulin and the insulin dose can often be lowered in this way. With four classes of
oral agents and insulin, it is now easier to control blood sugar levels for the millions
of diabetics around the world.

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