Thiazolidinediones (TZDs)

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Author: Judy Kohn, RN, BSN, CDE

Last Updated: Friday, September 21, 2007

Q: "How do Actos® and Avandia® work?"

A: Actos and Avandia belong to a class of drugs called Thiazolidinediones, popularly shortened to the term "TZDs", and also called insulin sensitizers.

First, a quick review:

How insulin works-it has 3 main roles:

Regulates the liver from releasing too much glucose (I like to say that insulin leans up against the door of the liver and only lets a little glucose out at a time). When there is enough glucose in the blood, insulin tells the liver to shut down its production of glucose.
Acts as a "doorman, or key" to open the doors of the cells (called receptors) and to allow glucose to enter the cells so the glucose can then be turned into energy.
Acts as a "traffic cop," directing some of the glucose to be stored back into the liver and the muscles, and if you eat more than you need, the excess energy is stored as fat.

There are 4 defects in type 2 diabetes that can be targeted by oral agents:

Insulin resistance: In essence, the body is unable to use insulin effectively. I explain in the link below that "it is as if there aren't enough doors on the cell wall, or the doors are stuck, or the lock has been changed, or else once the glucose gets into the cell it doesn't know what to do."
Increased glucose production by the liver: Usually, as soon as you begin eating, insulin tells the liver to "shut its door" and to quit releasing glucose, since you can now get glucose from the food you're eating. With diabetes, the liver doesn't shut off, so it continues to produce unnecessary glucose.
Decreased insulin production: Eventually, as diabetes progresses, the pancreas loses its ability to produce enough insulin-either it is delayed in releasing insulin, or it can't make enough-affectionately called a "pooped out pancreas."
Deficiency of GLP-1:Normally, within 10 minutes of eating, GLP-1 is released to enhance insulin secretion, slow stomach emptying, and suppress glucagon (to decrease glucose output from the liver).

How TZDs work:

TZDs mainly address the first bulleted defect in type 2 listed above: they help to decrease insulin resistance by making your body more sensitive to its own insulin so that the insulin can then move glucose from your blood into your cells for energy. These drugs also help to decrease the amount of glucose produced by the liver, which is the 2nd bulleted defect of type 2 listed above. Note: Because TZDs do not stimulate the pancreas to produce more insulin, then when used alone, they will not cause hypoglycemia.

TZDs are taken either once or twice a day, and they can be taken with or without food. Because Avandia and Actos are associated with a medication that had caused liver problems (Rezulin, which is no longer on the market), your doctor will check your liver function before starting this drug, then periodically thereafter. Call your doctor right away if you have any signs of liver disease: nausea, vomiting, stomach pain, lack of appetite, tiredness, yellowing of the skin or whites of the eyes, or dark-colored urine.

Side Effects:

Possible swelling (water retention).
Possible weight gain.
Possible anemia.
Increased risk of heart problems.
Increased incidence of arm, hand, and lower leg fractures in women.
If you take birth control pills, TZDs might make your birth control pills less effective in preventing pregnancy and may increase your chances of getting pregnant.

Cautions: While TZDs are used safely by many people, they are not recommended for people with certain heart conditions (such as congestive heart failure), liver problems, or pregnancy. Due to recent concerns about this class of drugs, please be sure to read the related question: " Concerns about TZDs."

Other effects or interactions:

It is always best to discuss your individual drug with both your doctor and your pharmacist. But in general, these drugs are considered safe and well tolerated by many people. Also you can read more about specific drug interactions from the websites listed below.

Combining TZDs with other diabetes drugs:

Due to the 3 defects in type 2 diabetes, it is common that you may eventually require more than one category of diabetes medication. Studies show that when needed, combining 2 or more diabetes pills with different mechanisms of action can be very effective. But remember that if you take a TZD along with a sulfonylurea, a meglitinide, or insulin, then there is the potential for hypoglycemia.

Conclusion:

Finally, just as you know there is "no free lunch", remember that meal planning, regular activity, and glucose monitoring are still the cornerstones of good diabetes management, and that diabetes pills are another tool to help you keep your diabetes in good control.

Be sure to discuss all your medications, side effects, safety precautions, and possible interactions with your physician.

Thiazolidinediones (TZDs)

How insulin works-it has 3 main roles:

There are 4 defects in type 2 diabetes that can be targeted by oral agents:

How TZDs work:

Side Effects:

Other effects or interactions:

Combining TZDs with other diabetes drugs:

Conclusion:

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