A Glitazone Primer | Levin Papantonio Rafferty - Personal Injury Law Firm

A Glitazone Primer

In order to understand Actos and Avandia are intended to treat Type II diabetes and how they have wound up causing seemingly unrelated health problems, it will be helpful to review some basic biology.


Most people take insulin for granted. This is a hormone, produced by a healthy pancreas, that regulates the metabolism of carbohydrates (saccharides) and fats (lipids).  Both of these play important roles in the conversion of food into usable energy as well as storage of that energy. 


When carbohydrates (in the form of starches such as grains and sugars from fruit and other vegetable sources) are consumed, they are converted and released into the bloodstream as glucose. This form of sugar is vital to our metabolic processes, and is a primary fuel for living cells. However, like many other substances, too much glucose in the blood can be toxic and lead to serious problems. This is where the hormone insulin enters the picture. The purpose of insulin is to remove excess glucose from the blood. In people with a normal functioning pancreas, insulin is released into the bloodstream in the proper amounts, when and as needed.


Here is where it gets a bit complicated. As you may know, hormones, such as insulin, function as biochemical messengers that carry signals to the body's cells (think of these as data streams). In order to receive those signals, cells have molecules known as receptors (similar to a computer Internet terminal or a cell phone receiver). These receptors are called peroxisome proliferator-activated receptors, or PPARs for short. When it comes to the regulation and metabolism of glucose, fats and proteins, there is a specific PPAR that biologists have identified with the Greek letter gamma (PPARG).


When a person's cells begin to develop insulin resistance, it is because the cells' PPARG receptors  have become "fatigued" and no longer do their job properly. The purpose of glitazone drugs is to "wake up" these PPARGs and get them functioning again.


Since the 1990s, there have been three types of glitazone drugs on the market, each of which has would up  causing serious side effects. Rosiglitazone is sold under the brand name Avandia. Because independent research has shown this drug to cause an increased risk of cardiovascular disease, it has been banned in the E.U. Not surprisingly, it is still marketed and prescribed in the U.S., albeit under significant restrictions.


Pioglitazone is the chemical name for the proprietary drug Actos, which has now been connected to an increased risk of bladder cancer. Sales of this drug have been suspended in France and Germany – but again, unsurprisingly, its use continues in the U.S. Amazingly, some endocrinologists have prescribed this for Type-I diabetics – and if you have understood the information presented here and in my previous post, you realize why this practice is questionable at best (generally, Type-I diabetics don't have a problem with their PPARG receptors).


A third medication, troglitazone, was introduce  by a Japanese company in the late 1990s and licensed for manufacture by the pharmaceutical corporation Parke-Davis for sale in the U.S. under the brand name Rezulin. Despite the fact that a medical officer spoke out about the drug's toxic effects on the liver, the FDA gave its approval in January 1997. Less than a year later, the drug was taken off the market in the U.K. - but it was three more years before it was removed from the U.S. market.





DeFronzo, R.A. "Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance. "New England Journal of Medicine, March 2011.


Krentz, A.J. and P.S Friedmann. "Type 2 Diabetes, Psoriasis and Thiazolidinediones." International Journal of Clinical Practice, March 2006.


Kumar, Vinay et. al. Robbins and Cotran Pathologic Basis of Disease, 7th Ed. (Philadelphia: Saunders, 2005).


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