You must have some insulin-making ability to be able to respond to an oral diabetes agent. If your body is not making enough insulin or the cells in your body are not able to correctly use the insulin you are making, and if simple control of dietary intake (or getting your body weight closer to normal) is not effective, you probably need an oral agent to help control your blood-glucose levels. If this does not work for you, then another choice of medication is made.

Many people think that if they are taking the pills they do not need to watch their dietary intake. This is not true. You must still eat spaced meals and one or more snacks each day and follow all the other parts of your self-care program. It is also important to check your blood-glucose levels to be sure that the medication is working to meet the goal of premeal blood-glucose levels of between 70-110 mg/dl (4-6 mmol) and two-hour postmeal (postprandial) levels of less than 150 mg/dl (8 mmol) (or at least less than 180 mg/dl (10 mmol)) and an overall goal of less than 7 percent for the HbA1c.

You must also be knowledgeable about the side effects of oral agents. These are hypoglycemia (low blood sugar), nausea, and vomiting. Yellowing of the skin (jaundice) and skin rashes have also been reported. Except for hypoglycemia, these side effects occur in fewer than 1 percent of people taking these medications. Metformin, Troglitazone, and Acarbose will not cause hypoglycemia when used alone but may do so when used with other agents. There are other side effects with these drugs, however. Metformin may cause upset of the intestinal tract, especially diarrhea. This is usually seen only at the start of treatment with this drug and usually goes away in 1 to 2 weeks. This problem can be minimized by starting the drug at low doses and giving the drug with food. Rezulin can cause damage to the liver with elevation of some enzymes in the blood called transaniminases. These enzymes should be monitored monthly for 8 months, then every 2 months, then at each regular office visits. Acarbose can also cause intestinal upset as it is especially bad in causing gas.

You need to be familiar with the interaction of your diabetes medication with any other medications you might be taking. Drinking alcohol while you are taking Clorpropamide may result in an Antabuse type of reaction (flushing of the skin, nausea, and vomiting). With the first-generation oral hypoglycemic agents, taking another drug during the same day may cause either the drug or the oral agents to work more or less effectively. Drugs that may interact with these agents include anticoagulants, birth-control pills, diuretics, steroids, and Dilantin (which raise the blood sugar), as well as some that lower blood sugar, including aspirin and some medicines used to treat high blood pressure (such as Inderal). Oral agents are not prescribed for children except as used in research programs in children with Type 2 diabetes, or for women who are pregnant or breast-feeding. If you are ill or having surgery, the physician may choose to have you take insulin for a period of time. You also need to be familiar with the time action of the oral hypoglycemic agents. This allows you to either predict or determine the potential for hypoglycemic episodes.

One short-acting oral agent is called tolbutamide (the generic name) or Orinase (the brand name). If the physician places the generic name on the prescription, you can often receive the product at its lowest cost. The generic pill is available in 500-mg tablets from the Barr, Danbury, Lederle, and Zenith drug companies. It starts working in 1 hour and is half used in about 5.6 hours; the total time it works in the body is approximately 6 to 12 hours. The recommended dosage is no more than 3 gm (or six 500-mg tablets) per day.

The intermediate-acting oral agents are acetohexamide (Dymelor) and tolazamide (Tolinase) from the first generation, and glipizide (Glucotrol), glimepiride (Amaryl), and glyburide (Micronase, DiaBeta, or Glynase) from the second generation (see Table 6-1). The first-generation pills were tested and put on the market in the 1950s and 1960s. The second-generation pills were tested in the United States and put on the market in the 1970s and 1980s.

Acetohexamide (Dymelor) -- Acetohexamide (Dymelor) comes in 250-mg and 500-mg tablets and is available from the Eli Lilly Pharmaceutical Company. This medication starts working in about 1 hour, and over half of its usefulness occurs within 5 hours. It lasts in the body for approximately 10 to 14 hours. The maximum dosage recommended is 1.5 gm (six of the 250-mg tablets or three of the 500-mg tablets) per day. If you have problems with improper functioning of your kidneys, this would not be a medication that your doctor would recommend.

Repaglinide (Prandin) -- Repaglinide (Prandin) is a new rapid and short-acting oral agent for diabetic control. This drug is of a different class of drug that can be used in people allergic to the other oral drugs, but it works the same way as the others. It acts more quickly than the other drugs so is given right before the meals. It keeps the after-meal blood sugar down well and then is gone rather quickly, so it doesn't hang around and cause low blood sugar later. It is very effective but has the inconvenience of having to be taken 3 to 4 times a day. It has the convenience of very few side effects and little hypoglycemia. It is also convenient in that the dose can be skipped if the meal is skipped. Other drugs last longer and may cause hypoglycemia if a meal is missed, but not so with this short-acting drug. Thus there is more flexibility of schedule with this drug. The doses of Prandin range from 1/5 mg three times a day with meals to 4 mg with each meal and at bedtime.

Tolazamide (Tolinase) -- Tolazamide (Tolinase) is an oral agent that is absorbed more slowly (its onset is 4 to 6 hours). If you have a tendency to absorb food slowly, then this oral agent might be recommended for you. It comes in 100-mg, 250-mg, and 500-mg tablets from the Upjohn Company. Half of the usefulness of this medication in your body occurs within approximately 7 hours. The maximum recommended dosage is 1 gm (ten 100-mg tablets, four 250-mg tablets, or two 500-mg tablets) per day. This product is also available as a generic through the Barr, Danbury, Lederle, and Zenith drug companies.

Glyburide -- Glyburide is a product available through the Upjohn Company (Micronase and Glynase) and the Hoechst-Roussel Company (DiaBeta). The tablet sizes are 1.25 mg, 2.5 mg, and 5 mg. The maximum dose recommended is 20 mg/day. Glynase is a more bioactive drug (i.e., it works slightly better). It is available in 3 mg and 6 mg tablets; top dose is 12 mg. These tablets are easily broken into two pieces. As with any other intermediate-acting oral agent, the dosages are usually divided (some before breakfast and some before supper) when 10 mg or more of medication is needed. The onset is 1.5 hours, and the total duration is around 24 hours. Half of the medication's usefulness may occur anywhere from 3.2 hours, for part of its chemical action, up to 10 hours for the rest of its half-life. Half of this medication is excreted in the urine and the other half through the bile in the liver, but caution is still encouraged for use in the elderly.

Glimepiride (Amaryl) -- Glimepiride is the newest sulfonylurea oral hypoglycemic agent. This drug has the advantage of being insulin sparing. Glimepiride works by making the available insulin more effective by it effects on muscle and fat cells and on the liver. The drug is taken once a day in 1-, 2-, and 4- mg tablet sizes. Starting dose is 1 mg/day. The dose can be increased every two to four weeks if the full therapeutic effect is not achieved. Maximum dose is 8 mg per day.

Glipizide (Glucotrol) -- Glipizide (Glucotrol) is a 5-mg or 10-mg tablet product developed by Pfizer but marketed by Roerig Company. Its action begins an hour after it is swallowed. The half-life is 3.5 to 6 hours, and it may remain in the body for anywhere from 12 to 16 hours. It is recommended that a total of no more than 40 mg be taken in a day and that the medication should be taken on an empty stomach (that is, about 30 minutes before a meal). If more than 15 mg are needed, the dose should be divided. Glucotrol XL has more recently been made available. The XL stands for extended life or longer-lasting medication. The top dose of Glucotrol XL is 20 mg. Although this medication is changed in the liver to an inactive form, caution for use in the elderly is recommended.

Acarbose (Precose) -- This drug works in the small intestine to slow the breakdown of carbohydrates, particularly complex carbohydrates. Acarbose slows down the natural breakdown of starches, dextrins, maltose, and sucrose to absorbable monosaccharides. It is therefore most effective for people with high glucose levels after eating. Acarbose is taken just before meals, or with the first bite of each meal. Doses begin with one 25-mg dose with the first bite of a meal. Side effects include abdominal pain, diarrhea, and flatulence. Acarbose is not to be used with patients who have inflammatory bowel disease, colonic ulceration, or partial intestinal obstruction. It can be used alone or in combination with any of the other drugs and/or insulin.

Troglitazone (Rezulin) -- Troglizatone is a new oral anti-hyperglycemic agent that acts to decrease insulin resistance. Its complete action is unknown, but it is thought to stimulate the production of a protein involved in the transport of sugar through the cell membrane from the blood to the interior of the cell for use. It takes 3 to 6 weeks for the medicine to have much effect on the blood-glucose level and may take as much as 12 weeks for it to have its full effect. The medicine is taken with food to enhance its absorption. It can be taken with any meal but needs to be taken only once a day. It is absorbed in 2 to 3 hours and may be taken at any meal. If it is missed at the usual meal, it may be taken at the next meal. If it is missed on one day, it should not be doubled the next day. More than 85 percent of the medicine's waste products are removed through the intestinal tract, and only a little over 3 percent is released through the urine. It is not recommended for pregnant or breast-feeding women or people with severe heart disease. It is recommended for persons with Type 2 diabetes. In the future, it will be used alone or with other oral agents, but it has not yet been approved for this use. It may be used alone or with other oral anti-diabetes drugs or with insulin. A person would start with 200 mg once daily with a meal. After 2 to 4 weeks, the dose may be increased to 400 mg (usual dose) or later up to the maximum dose of 600 mg. If the person is already on insulin, it is recommended that after Rezulin is started, insulin may be decreased to 10 to 25 percent or more when fasting blood sugars are less than 120 mg/dl (7 mmol). One value of this drug is that it is remarkably free of side effects, even at maximal doses.

There has been a lot of publicity recently about this drug. Newspapers, TV, and radio have publicized the dangers, and some have petitioned the FDA to recall the medication. Most of these people are not aware of the grave dangers of diabetes so they do not balance the benefits versus the dangers. The danger that has been publicized is possible damage to the liver. There have been 33 deaths from liver disease attributed to this drug over a three-year period. There are several million people taking the drug so the possibility of fatal liver disease is very small compared with the dangers of poor blood sugar control. All of these deaths occurred early in the use of the drug when patients were not being monitored for this problem. Indeed many of the people who developed liver disease and died had liver disease prior to taking the drug so they should not have been started on it. Since this information became available over a year ago, we have been monitoring patients carefully, and no deaths have occurred since. The liver damage from the drug is rare, and when picked up early and the drug is stopped, it is reversible. The information made public recently in the lay press was over a year old and had been corrected by the medical profession and the company. This type of late press and presenting only a year-old story without checking on the more recent facts is irresponsible and unfair to the people who need and are doing well on the drug (and have been monitored properly). Monitoring is by a simple blood test to measure the transaminase enzymes. These enzymes should be measured before starting the drug, monthly for the first 8 months of therapy, then every 2 months, and then at every regular doctor visit. If this is done, there is little or no danger from this drug. It is a highly effective drug and has vastly improved diabetes control in thousands of patients and should continue to be used. Be sure, though, if you are taking the drug that your doctor is monitoring your enzyme levels and that the drug is stopped if they begin to rise.

Oral hypoglycemic and anti-hyperglycemic agents have an important place in the medical management of diabetes. They can be used alone or in combination with each other and/or with insulin. When the blood sugar is no longer controlled by the maximum recommended amount of an oral medication, there is no other recourse than to administer insulin. If more of the oral agent is taken than is recommended, it is very possible that the person could become quite sick.