What is Your Treatment Zone?

Everybody is talking about Enter The Zone these days. They are referring to the popular book on nutrition and diet by Barry Sears. But there are other zones as well – the “treatment zones” for type 2 diabetes. Knowledge of these zones will help you better understand how and why your particular treatment program was designed.

Recently, metformin (Glucophage), acarbose (Precose), and lispro insulin (Humalog) have all been approved for the treatment of type 2 diabetes. Soon to be available is troglitazone (Rezulin). With this ever expanding list of drugs used to treat diabetes, some people are left wondering where these new treatments fit into their own plan. To help you understand the current therapy options, see chart A on page one. These zones are not absolute or fixed, but are guides to help you understand where these new therapies belong in the treatment algorithm (flow chart) for type 2 diabetes.


Before delving into the “treatment zones” let’s review the drugs currently available. The mainstays of treatment for people with type 2 diabetes over the past few decades have been the sulfonylureas (SU). The majority of people on SU take one of three drugs from this class: glyburide (Micronase, DiaBeta), glipizide (Glucotrol, Glucotrol XL), or chlorpropamide (Diabinese). A new SU, glimepiride (Amaryl), was recently introduced in the United States.

The main effect of all the SUs is to increase insulin production by the pancreas. People most likely to respond to SUs tend to have had the disease fewer than five years, are over 40 years of age, are overweight and have blood glucose (BG) readings less than 200 mg/dL. Additionally, people who have never required insulin or need less than 40 units per day have better responses to the SUs. On average, the SUs can reduce BG levels by 50-60 mg/dL with corresponding decreases in HbA1c of 1-2%.

The occurrence of hypoglycemia and weight gain are the primary side effects of the SU. It is important to be able to recognize the signs and symptoms of hypoglycemia if an SU is taken, and the products needed to treat low BG (e.g., glucose tablets) should be readily available.

Alpha-Glucosidase Inhibitors

One of the newer classes of drugs used to treat type 2 diabetes is the alpha-glucosidase inhibitors. These inhibitors partially prevent the digestion of complex carbohydrates (starches) and the subsequent absorption of glucose in the body. This tends to lower the rise in BG seen after eating a meal. Acarbose (Precose) can lower BG by 20 mg/dL and decreases HbA1c by 0.6%. It is also effective in combination with metformin, sulfonylureas and insulin.

The most common side effects of acarbose are flatulence (gas), diarrhea and abdominal pain. These side effects tend to lessen the longer the drug is taken. Acarbose would not be a wise choice for people with inflammatory bowel disease, colon ulcers or other chronic conditions involving the stomach or intestines.


Metformin (Glucophage), available in the United States for the past two years, works entirely differently than the SU or acarbose. Metformin primarily decreases the production of glucose by the liver and increases the action of insulin on muscle. This unique medicine tends to lower BG levels by 60 mg/dL, and decreases HbA1c up to 2%.

Besides its effects on BG, metformin tends to lower blood lipids (triglycerides, LDL-cholesterol – the bad cholesterol – and total cholesterol levels). Another added benefit of metformin is that it increases the levels of HDL-cholesterol (the good cholesterol). Also, most people on metformin lose weight, another favorable effect of this drug.

Side effects of metformin include abdominal bloating, nausea, cramping and diarrhea. These side effects may not occur at all or may develop after a few months of therapy. But, they occur most often when therapy is first started and usually go away or lessen in frequency the longer the drug is taken. Taking the medication with food decreases the likelihood of side effects.

Because of its ability to reduce blood glucose levels while not causing weight gain, and its beneficial effects on lipid levels, metformin is a reasonable medicine for people who are obese or have high blood lipid levels. One side effect that is not associated with metformin therapy is hypoglycemia. Although metformin can be used safely with the sulfonylureas, hypoglycemia can occur with this combination.


Insulin is the natural hormone produced by the pancreas to lower BG, and up to a third of all people with type 2 diabetes use insulin.

The various types of insulin vary in their length or duration of action. Short-acting insulins include regular and lispro, with lispro having the quickest onset of action. Intermediate insulins include NPH (Humulin N, Novolin N) and lente (Humulin L, Novolin L). Ultralente (Humulin U, Novolin U) is a long-acting insulin. Depending on your specific BG levels, you may or may not have to take insulin. Also, some people on insulin may be on a single type of insulin, and some may be on combinations of the various insulins.

Lispro can be used by itself or with orally available blood glucose lowering drugs (SU, acarbose, metformin). A possible advantage of lispro insulin is that it works faster than regular insulin, thus it can be conveniently taken near mealtime and better control of BG levels may be achieved. Possible side effects of lispro, common to all insulins, are hypoglycemia and weight gain.

What Zone Are You In?

So which zone are you in, and what are your treatment options within each zone? The zone that you are in depends upon what measures are needed to keep your BG under control. Proper control consists of a fasting BG between 120 and 140. If after two to three months your fasting BG is over 140 or your HbA1c is over 8%, then something is missing from your treatment plan, and you will most likely need to move to the next treatment zone.

Zone 1

Zone 1 is the zone that should be familiar to all people with diabetes, the “nondrug therapy zone.” Nondrug therapy includes nutrition, exercise and formal diabetes education. Home BG monitoring may also be included in this area. It is important to remember that this zone applies to all type 2s. This means that even though you may be receiving oral drugs or insulin to help control your diabetes, you need to continue to adhere to the principles of zone 1.

Zone 2

As we move into zone 2, the “single drug zone,” our treatment options increase. The two critical questions that need to be answered are: (1) are you obese or do you have high blood lipids? and (2) what is your fasting BG level? How these are answered will determine which part of zone 2 you end up in, thereby influencing the treatment that is best for you.

Basically, if you answered yes to one or both parts of question 1 then your options include using either metformin or acarbose. These are options in area A of chart A. If you answered no, then your options include SU or acarbose, area B of chart A.

Which of those two drugs to use in each area will depend on your fasting BG level (see chart for details).

Zone 3

Zone 3 is the “combination drug zone.” Since therapy with a single oral drug has failed, then a second oral drug is initiated along with the drug you were taking while in zone 2. If in area A and on acarbose, then metformin is added. If on metformin previously, then an SU may be added. In area B an SU is added, if on acarbose, and conversely, if on an SU either acarbose or metformin may be started. In general, if you are in area B and already on an SU and you are within 20 mg/dL of your BG goal then acarbose is most likely to be added. If you are over 20 mg/dL of your BG goal, then metformin is probably a better choice.

Zone 4

Zone 4, the “oral drug plus insulin zone,” requires that one of the oral drugs from zone 3 be discontinued and replaced with the administration of insulin. If in area A, metformin is usually recommended along with either an intermediate (NPH) or short-acting insulin (lispro, regular). If in area B then the SU is retained, and insulin is added. In many instances the NPH insulin will be given in the evening or at bedtime, and short-acting insulin is taken three times daily near mealtime.

Zone 5

When in zone 5, or the “insulin zone,” areas A and B disappear. In this zone, various types (short-, intermediate-, and long-acting) and combinations of insulins may be used. The type and time of insulin administration is best determined by your physician and your individual response to therapy.

Rezulin can be included in this zone once it is put on the market. But, because of the relatively small number of studies at this time, further recommendations should be left up to your personal physician.

These “treatment zones” will help you understand the decisions that need to be considered and the therapy options available to you, your physician and others involved in your care to successfully manage your diabetes. By adhering to the principles in zone 1 and each consecutive zone, hopefully you will stay in the “my diabetes is under control zone.”

Dr. Stephen Setter, clinical instructor at Washington State University’s College of Pharmacy, wrote this piece with the generous help of John R. White, PharmD.

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