Angelica Bottaro is a writer with expertise in many facets of health including chronic disease, Lyme disease, nutrition as medicine, and supplementation. 
Isabel Casimiro, MD, is board-certified in internal medicine and works as an endocrinologist at the University of Chicago.
Thiazolidinediones (TZDs) are oral diabetes medications that make your body more sensitive to insulin. They can be used alone or with other medications to help you control your blood sugar. While they are often effective, especially when first-line diabetes treatments aren’t helping, there are downsides and contraindications to discuss with your healthcare provider.
This article covers how thiazolidinediones work, their side effects, and contraindications.
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Thiazolidinediones belong to a class of drugs known as heterocyclic compounds. They are taken orally and used to treat type 2 diabetes by making a person’s body respond better to the insulin they produce. Insulin is a hormone produced by the pancreas. It is used by the body to move glucose (sugar) from the blood into cells, where it is used for energy.
Currently, only two types of TZDs are available:
TZDs are sometimes combined with other diabetes drugs, such as Metformin, and can come in combination pills. Some drugs are used together because doing so offers more effective disease management. 
TZDs encourage higher insulin sensitivity. They do so by activating the peroxisome proliferator-activated receptor-y (PPAR-y). PPAR-y plays a role in metabolism, and when it is activated, glucose, protein, and fat are better utilized in the body.
In helping the body better use those nutrients, it becomes more sensitive to the insulin produced by the pancreas. Since type 2 diabetes is caused by lower insulin sensitivity, TZDs reverse those effects by encouraging proper functioning of the body’s metabolism and improving its ability to use insulin. 
Insulin sensitivity refers to how well the body can use the hormone to get glucose into cells. When a person has normal insulin sensitivity, blood glucose is managed effectively.
The dose a person takes will depend on what TZD they use. For example, pioglitazone is typically taken once per day at 15, 30, or 45-milligram (mg) doses. Rosiglitazone dosing can be different and is taken either once or twice per day. People taking this medication are started on two to four milligrams daily and will gradually increase if their body doesn’t respond to the lower dose. The maximum daily dose of rosiglitazone is eight milligrams.
A specific type of blood test, known as the HbA1c test, monitors a person’s average blood sugar levels over two to three months. HbA1c should be monitored at least twice a year when taking thiazolidinediones to check blood glucose and see if the dosage needs to be adjusted.
As with all medications, TZDs come with various side effects. Some of the mild side effects can include:
These symptoms are typically present when a person begins treatment and will subside as the body adjusts to the new medication. However, if they persist, you should contact your healthcare provider.
Other more severe side effects can include:
These symptoms require prompt medical evaluation as they could signify a severe adverse reaction to the medication.
Sometimes, TZDs can lead to liver problems requiring immediate medical attention. Symptoms that could indicate a liver issue while taking this medication include:
Because TZDs can cause serious side effects and come with many warnings, people taking these drugs should continuously monitor their blood sugar levels and overall health.
For example, when taken with other diabetes medications, a person may increase their risk of developing hypoglycemia, which is dangerously low blood sugar. Monitoring sugar levels can help avoid that and other complications. 
There are several contraindications and warnings associated with TZDs. That is why in 2007, they were given a black box warning by the U.S. Food and Drug Administration (FDA). However, in 2013 after new research about TZDs was available, the black box label was removed.
The warnings were initially added to TZDs because they were shown to increase the risk of heart failure, especially in people with a history of heart failure or a cerebrovascular ischemic event, which occurs when the oxygen supply to the brain is cut off or lowered.
Edema (swelling caused by fluid retention) can also occur in people taking TZDs. Edema can also cause or increase the risk of heart failure.
Another contraindication that can occur in people taking TZDs involves bone health. People taking these medications have an increased risk of bone fractures. Pre- and post-menopausal women have a greater risk of a fracture injury while taking TZDs.
The FDA-issued black box warning is given to medications with the highest likelihood of dangerous or severe effects. It is considered the highest safety warning.
TZDs are drugs used to treat type 2 diabetes. They make the body more sensitive to insulin, allowing the sugar in the blood to transfer more easily into cells for energy. There are two types of TZDs on the market; they can be used alone or in combination with other diabetes drugs for better disease management.
While the drugs are effective, they come with mild and severe side effects that people should be aware of. Everyone who takes TZDs should monitor their blood sugar levels regularly and watch for side effects or adverse symptoms.
Choosing the proper medication to manage diabetes isn’t always easy. Even the safest drugs come with uncomfortable side effects. The critical thing to remember is that your healthcare provider wants what’s best for you when prescribing you medications. If you have been prescribed TZDs and have concerns, bring them up with your healthcare provider.
People with type 2 diabetes can take thiazolidinediones. The dosage will range depending on the type. Typically, they are taken orally once or twice daily. They can be taken with or without food.

Water retention is a side effect of taking thiazolidinediones. Water retention due to thiazolidinediones is caused by an increase in fluid reabsorption in a tube found in the filtering units in the kidneys. Sometimes, it can be severe enough to warrant stopping the medication.
Weight gain while taking thiazolidinediones is a common side effect of the medication. Sometimes, it can be challenging to prevent it because it is caused by the same mechanism of action that helps the medication work. Maintaining a healthy diet and getting enough exercise may help to limit weight gain while taking the medication. 
Arnold SV, Inzucchi SE, Echouffo-Tcheugui JB, et al. Understanding contemporary use of thiazolidinediones. Circ Heart Fail. 2019;12(6):e005855. doi:10.1161/CIRCHEARTFAILURE.118.005855
The Johns Hopkins Patient Guide to Diabetes. Thiazolidinediones. Insulin sensitivity.
National Institute of Diabetes and Digestive and Kidney Diseases. The A1C test & diabetes.
Medline Plus. Pioglitazone.
Hickson RP, Cole AL, Dusetzina SB. Implications of removing rosiglitazone's black box warning and restricted access program on the uptake of thiazolidinediones and dipeptidyl peptidase-4 inhibitors among patients with type 2 diabetes. J Manag Care Spec Pharm. 2019;25(1):72-79. doi:10.18553/jmcp.2019.25.1.072
Lebovitz HE. Thiazolidinediones: the forgotten diabetes medications. Curr Diab Rep. 2019;19(12):151. doi:10.1007/s11892-019-1270-y
By Angelica Bottaro
Angelica Bottaro is a professional freelance writer with over 5 years of experience. She has been educated in both psychology and journalism, and her dual education has given her the research and writing skills needed to deliver sound and engaging content in the health space.

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