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TZD Side Effects

Thiazolidinediones, or TZDs, are drugs that can be taken to treat Type II diabetes. One of the problems people with Type II diabetes face is that their bodies become resistant to insulin. Because TZDs lower your resistance to insulin, you feel the effects of the insulin more. This allows the insulin to function as it's supposed to and transport glucose from the blood into the cells to be converted into energy. TZDs also limit the amount of insulin the liver can produce.

  1. Edema

    • The protein peroxisome proliferator-activated receptor (PPAR) gamma is found in different parts of the body, including the kidney and heart. PPAR gamma is in the collecting duct of the kidney, which is responsible for metabolizing fluids. A 2005 University of Utah study showed that when TZDs stimulate PPAR gamma in mice, the distal nephron is also affected. The distal nephron is the part of the kidney that regulates sodium. It determines how much sodium should pass through the body via urine and how much should be reabsorbed. When the balance is disturbed, it leads to fluid retention, or edema. In some cases, this leads to potentially-fatal pulmonary edema.

    Bone Problems

    • PPAR gamma plays an integral role in controlling both the sugar levels and the bone mass in the body. TZDs are meant to have an impact on this protein in order to affect sugar levels, but an unwanted side effect is that they also affect bone mass. A 2006 study by Dr. Ann V. Schwartz and her colleagues noted that TZDs lead to bone loss, particularly in women and more specifically in older women. A decrease in bone density increases the risk of a fracture and unnecessary stress on the skeleton.

    Heart Problems

    • In 2007, Dr. Steven Nissen released the results of his study showing that the TZD rosiglitazone (Avandia and Actos) leads to edema, which can then lead to congestive heart failure. The study showed a significant increase in the risk of congestive heart failure, but not an increase in the risk of death due to cardiac problems. While the study has been criticized by some parts of the medical community, it led to new (more serious) warning labels on these drugs. The boxed warnings state that the drugs could lead to congestive heart failure or worsen existing heart conditions.

    Liver Failure

    • The TZD troglitazone has been linked to drug-induced hepatitis, which is an inflammation of the liver. There are various types of hepatitis, with the most serious forms resulting in liver failure or requiring a transplant. Although troglitazone is no longer available, it is in the TZD family of drugs, meaning the doctor may perform tests on the liver before starting a TZD regimen and throughout the course of treatment. Anyone taking TZDs should tell their doctor if they have abdominal pain, dark-colored urine, nausea, or vomiting.

    Weight Gain

    • Under normal circumstances, when you need energy, the body sends a message to retrieve triglycerides (TGs) from fat cells so they can be converted into glycerol and then into sugar glucose to use for energy. TZDs bind with PPAR gamma leading to the creation of glycerol kinases in the cells. These in turn combine with fatty acids to form TGs. The glycerol kinases forms new fat cells at a faster rate than the body uses them.

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