Thiazolidinediones for diabetes treatment side effects, safety, danger, caution
December 12 2016 by
Ray Sahelian, M.D.

The role of thiazolidinediones -- such as rosiglitazone and pioglitazone -- in the treatment of Type 2 diabetes and lowering blood sugar is established, but whether taking these drugs helps reduce overall mortality has yet to be determined. Patients with diabetes, especially women, who take thiazolidinediones, which include commonly prescribed drugs such as Avandia and Actos, may have an increased risk of developing cancer and suffer other health problems. Avandia is the product name for rosiglitazone. There are natural approaches to treating type 2 diabetes. See diabetes for natural treatment options. If you would like to reduce your blood sugar by eating less, consider Diet Rx.

Thiazolidinediones side effects, adverse reactions, danger, safety
Liver damage and fluid retention, which can aggravate pre-existing heart failure, are the most important side effects. A meta-analysis in October 2007 finds an increase in congestive heart disease for patients taking the thiazolidinediones rosiglitazone and pioglitazone. Recent studies indicate these drugs can increase the risk for heart attacks and bone fractures.

Higher risk for cancer
The FDA reaffirmed its warning in 2016 on the possible risk of bladder cancer associated with use of the type 2 diabetes drug pioglitazone.

Danger of thiazolidinedione drugs and heart attacks
Older patients treated with the diabetes drugs known as thiazolidinediones (which include rosiglitazone) have a significantly increased risk of heart attack, congestive heart failure and death, compared with the use of other hypoglycemic drugs.

Thiazolidinedione drugs increase risk for bone fracture
Two thiazolidinediones drugs prescribed by doctors to lower blood sugar and treat diabetes -- pioglitazone and rosiglitazone -- increase the risk of bone fractures. Patients who use pioglitazone and rosiglitazone drugs for a year or longer are more than twice as likely as nonusers to fracture a bone. Pioglitazone and rosiglitazone are also known by the trade names Actos and Avandia. The use of these drugs is associated with bone fractures of the hip and wrist, and the elevated risk is seen in both men and women, independent of age. Archives of Internal Medicine, April 28, 2008.

Mechanism of action of thiazolidinedione medications
The mechanism of action involves binding to the peroxisome proliferator-activated receptor-gamma, a transcription factor that regulates the expression of specific genes especially in fat cells but also other cell types such as endothelial cells, macrophages and monocytes, vascular smooth muscle cells and colonic epithelium. Thiazolidinediones have been shown to interfere with expression and release of mediators of insulin resistance originating in adipose tissue (e.g., increased free fatty acids, decreased adiponectin) in a way that results in net improvement of insulin sensitivity (i.e., in muscle and liver). Prevention of lipid accumulation in tissues critical to glycaemia such as visceral adipocytes, liver, muscle and beta-cells at the expense of lipids accumulating at the less harmful subcutaneous site may be central to their net metabolic effect.

Thiazolidinediones and diabetes prevention
The sustained beneficial effect of troglitazone on beta-cell function in women with previous gestational diabetes in addition to the insulin-sensitizing properties point to an important role of this class of drugs in the prevention of Type 2 diabetes. Original safety concerns based on animal and in vitro studies (e.g., fatty bone marrow transformation, colonic cancer, adipogenic transdifferentiation of blood cells) remain potential future problems we may discover.
   Comments: Since this was written a few years ago, the risk of these drugs causing an increased risk for heart attacks and bone fractures has become apparent.

J Clin Res Pediatr Endocrinol. December 15 2013. Effect of pioglitazone on the course of new-onset type 1 diabetes mellitus.  Type 1 diabetes mellitus (T1DM) is caused by insulin deficiency resulting from progressive destruction of β cells. The histological hallmark of the diabetic islet is mononuclear cell infiltration. Thiazolidinediones (TZDs) activate PPARg and enhance the actions of insulin. In this pilot study, pioglitazone did not preserve β cell function when compared to placebo.