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Expanding Options for the Treatment of Type 2 Diabetes

Expanding Options for the Treatment of Type 2 Diabetes

Oral Medication Therapy Review

By Shay L. Reichert, Pharm.D., BCPS, Ph.C., CDE
02 3When a person is first diagnosed with type 2 diabetes, changes in lifestyle are usually recommended. Initially, the changes in diet and exercise are able to control the blood glucose, but a majority of people eventually needs some additional help from medications. Just a few years ago, this article would have been very brief since only two choices were available: oral sulfonylureas or insulin. Exciting progress in drug development has resulted in several other options. Here's a brief review of the current medication therapies.


Oral Sulfonylureas
Oral sulfonylureas (SU) work by stimulating the pancreas to pump out more insulin, resulting in lower blood glucose levels. Several medications belong to this class, which is divided into two generations. The second generation is thought to have fewer interactions with other medications and lesser potential for side effects. These are most commonly given one or two times a day. All SU should be taken with breakfast or the first main meal of the day, with the exception of glipizide. Food slows down the amount of glipizide that is absorbed; therefore, it works best when taken 30 minutes before a meal. The main side effects of SU are hypoglycemia (low blood glucose) and weight gain. Other adverse effects include stomach disturbances and rash. Chlorpropamide has the longest duration, and it should be used with caution by persons over 65 years of age or those with kidney problems.


Meglitinide
Repaglinide (Prandin¨) is a meglitinide, which is the newest class of medications. It works similarly to SU by stimulating the pancreas to release insulin. The main differences are its action time (it begins to work within 15 to 30 minutes of taking it), and its duration (it lasts only 2 to 3 hours). Repaglinide should be taken just before eating, and it is most effective when taken at least three times a day. If you skip a meal, the dose of repaglinide should be skipped. Likewise, if you eat an extra meal, then an extra dose should be taken. The maximum dose is 4 mg per dose with a maximum daily dose of 16 mg. Since it works like SU, its main side effects are hypoglycemia and weight gain.

Biguanide
Metformin (Glucophage¨) is the only biguanide currently approved in the United States. Metformin works mainly by decreasing the liver's production of sugar. Food slows down the absorption of metformin, but since its major side effect is stomach upset, most people take it with food. A rare, but life-threatening side effect is a condition known as lactic acidosis, which is a metabolic complication due to metformin buildup. New guidelines exist to decrease the chance of this occurring. Metformin should be avoided by people with kidney problems, liver disease, a history of lactic acidosis, and congestive heart failure requiring medication therapy. People who are pregnant or binge drink alcoholic beverages also should abstain. If you are taking metformin and have any of the above, you should contact your health care provider to further discuss this matter. The contraindications are a reflection of conditions that increase the risk of lactic acidosis, not a reflection of conditions caused by metformin. In certain situations, metformin should be stopped prior to a medical procedure or during certain illnesses. It is very important to tell all of your health care providers about your current medications. This can be accomplished easily by always carrying a list of your medications in your wallet.
Significant advantages of metformin include no hypoglycemia when it is used alone, lack of weight gain, and some beneficial effects on cholesterol levels. Metformin is usually taken one or two times a day and the usual maximum effect is achieved by 2000 mg per day. When given to appropriate candidates, metformin is a very safe and effective medication.

Thiazolidinediones
At this time, troglitazone (Rezulin¨) is the only thiazolidinedione approved in the United States. In the near future, two others will join this class. Troglitazone works mainly by helping the muscle cells take in insulin and sugar. It is known as an insulin sensitizer. Food helps more troglitazone become available to the body. It should be taken with food, preferably the largest meal, and it is dosed once a day. When troglitazone is used by itself, it does not cause hypoglycemia. A rare but serious side effect is idiosyncratic liver failure, which means that we cannot tell who will develop this problem. However, guidelines also exist to monitor for this side effect. During the first year of therapy, liver function should be checked every month for eight months, then every other month. After the first year, liver function should be checked periodically. Any signs of liver damage such as nausea, vomiting, abdominal pain, fatigue, anorexia or dark urine should be reported immediately to your health care provider. Troglitazone also interacts with other medications by speeding up their metabolism in the liver. This interaction is known to occur with oral contraceptives containing ethinyl estradiol and norethindrone. Troglitazone lowers the amount of oral contraceptives in the blood stream, thus potentially causing an unexpected pregnancy. Other medications that may also interact include astemizole, calcium channel blockers, cisapride, corticosteroids, cyclosporine, tacrolimus, triazolam, trimetrexate, and some HMG-CoA reductase inhibitors. Once again, this illustrates the importance of knowing your medications. Contact your health care provider or your pharmacist to rule out the potential of taking interacting medications.


Alpha-Glucosidase Inhibitors
Alpha-glucosidase inhibitors work by slowing down the absorption of complex carbohydrates. Acarbose (Precose¨) and miglitol (Glyset¨) are the two agents available in this class. They should be taken with the first bite of the meal to be effective. The major side effect is stomach disturbances resulting in the need to slowly increase the dose upward as tolerated. Acarbose has a new warning: it may cause liver dysfunction, and liver function should be checked every three months during the first year, then periodically. Miglitol does not have this information.
Combinations of the above agents may be utilized to keep the blood glucose controlled. The addition of insulin may also be necessary to reach target goals. Several of the medications take 1 or 2 weeks to reach their maximum effectiveness. To see the best results, you must take your medication on a regular basis.

Tips
  • Take your medications the same time every day.
  • Coordinate your medication schedule around your daily schedule.
  • Make taking medications a habit.
  • Buy and use a pillbox. Avoid the "did I take it?" question.
  • Mark your calendar after a dose is taken.
  • Know why it is important to take the medication. Another problem occurs when the prescription for the agents listed above is not filled.
  • This occurs for various reasons: Belief that "I just need to make some more changes to lifestyle"- even though these attempts no longer work
  • Feeling that "I don't need another medication!"
  • Fear of side effects
  • Lack of information regarding importance of blood glucose control
This occurs for various reasons:
  • Belief that "I just need to make some more changes to lifestyle"- even though these attempts no longer work
  • Feeling that "I don't need another medication!"
  • Fear of side effects
  • Lack of information regarding importance of blood glucose control
These arguments are important to acknowledge and discuss with your health care team who may include a dietitian, nurse, pharmacist and physician. If you know that you will not have the prescription filled or that you can not fit three doses a day into your schedule, tell your health care provider. Your health care provider truly wants to help you gain control of your blood glucose. You then have to buy into your treatment plan. By playing an active role in your own health care, you can achieve better results. You have made the first step by reading this article to increase your knowledge. Congratulations!

Shay L. Reichert is a content manager for healthanswers.com. In previous positions, she worked with patients and other health care professionals to maximize the effectiveness of medication regimens as a pharmacotherapy specialist. She also speaks nationally for the American Association of Diabetes Educators.

Reprinted with permission from Live Well

Date written: April 9, 1999
Date reviewed: October 24, 1999


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