I know that many people who have type 2 diabetes dislike taking any type of medication for their condition. This may be because they already take medication for other conditions, such as high blood pressure, or it might be because they feel they should be able to manage their diabetes through healthful eating, weight management and exercise. The last point is a good one, and certainly, in many cases, type 2 diabetes can be controlled through lifestyle measures. But not always. It really boils down to whether you’re meeting your blood glucose and A1C goals with what you’re currently doing. If you’re not, it’s time to talk with your healthcare team about what you can do; don’t be surprised or feel like you’ve failed if medication is the next step.
What are thiazolidinediones?
If you thought pronouncing “sulfonylureas” was a challenge, try “thiazolidinediones” (THIGH-ah-ZO-li-deen-DYE-owns). It’s a bit tricky, so for our purposes, I’m going to shorten it up and use the abbreviation “TZDs.” They’re also called “glitazones.” TZDs are not hypoglycemic agents — in other words, they don’t cause the pancreas to release insulin like sulfonylureas and meglitinides do. TZDs are known as “insulin sensitizers.” They work to lower insulin resistance, which is a key problem for people who have type 2 diabetes. By lowering insulin resistance, the insulin that your body makes can work better to move glucose from the blood into cells to be used for energy. Also, TZDs reduce the amount of glucose made by the liver.
The two TZDs available are pioglitazone (brand name Actos) and rosiglitazone (Avandia), and they both were approved in 1999. TZDs also are available in combinations with other diabetes pills. Studies show that TZDs may lower A1C levels from 0.5% to 1.4%. TZDs may be taken on their own or in combination with other diabetes medicines, including insulin.
How are TZDs taken?
Like other diabetes pills, TZDs are usually started at the lowest dose with gradual increases, as needed to achieve target glucose and A1C goals. They are taken once or twice daily with or without a meal. Pioglitazone is taken once a day, in doses ranging from 15 to 45 milligrams (mg), whereas rosiglitazone may be taken twice a day, in doses ranging from 2 to 8 mg.
What are the side effects of TZDs?
One of the main side effects of TZDs is fluid retention and edema (swelling caused by excess fluid), especially in people who take insulin. This fluid retention may increase the risk for heart failure. Weight gain is a concern, as well, not just because of fluid retention, but because TZDs may cause an increase in body fat.
Low blood sugar (hypoglycemia) is unlikely to occur in people who take TZDs unless they are also taking insulin or diabetes pills that can cause lows.
Several studies have linked rosiglitazone (but not pioglitazone) to an increased risk for having a heart attack. For this reason, in 2011, the FDA ordered a restriction on the use of drugs containing rosiglitazone, with strict criteria in place for prescribing. In 2013, the FDA reevaluated the most recent data and determined that rosiglitazone did not pose an increased risk for heart attack, and removed the restrictions. Troglizatone (Rezulin), one of the first TZDs, was recalled in 2000 after it was shown to cause liver damage.
Pioglitazone has been linked to an increase risk for bladder cancer, especially when taken for two years or more. For this reason, pioglitazone is no longer prescribed in France and no new prescriptions for this drug are issued in Germany. Pioglitazone may also raise the risk for bone fractures in women.
What else should you know about TZDs?
TZDs may cause ovulation in premenopausal women who do not ovulate. If you fall into this category, be sure to use birth control while taking these drugs.
Pioglitazone may raise HDL (“good”) cholesterol levels and lower triglyceride (blood fat) levels.
TZDs should not be used in pregnant or breastfeeding women, or in children.
They also shouldn’t be used in anyone who has a history of heart failure or liver disease.
If your doctor prescribes a TZD for you, you’ll need to let him know of any side effects, especially fluid retention, shortness of breath, or muscle aches. You’ll also need to have liver function tests periodically.
Want to learn more about the role of medicines in treating diabetes? Read the rest of diabetes educator Amy Campbell’s eight-part series on diabetes drugs, covering metformin, sulfonylureas, meglitinides, DPP-4 inhibitors, SGLT2 inhibitors, alpha-glucosidase inhibitors, bile acid sequestrants and dopamine receptor agonists, non-insulin injectable diabetes medications, and insulin.