Type 2 Diabetes Drug Faces Uncertain Future

Avandia is on The Hot Seat

Among a dozen diabetes medications, GlaxoSmithKline’s Avandia (rosiglitazone) has recently drawn scrutiny by the FDA due to adverse side effects on the cardiovascular system. To make matter worse, the company is being subpoenaed by the US Department of Justice over its development and marketing practices for Avandia over a decade.  In 28 October’s Nature reported that:

In its third-quarter earnings report released on 21 October, drug giant GlaxoSmithKline (GSK) revealed that it is being subpoenaed by the US Department of Justice over the company’s development and marketing practices for the diabetes drug Avandia (rosiglitazone). The company, headquartered in London, came under fire in July when a US Senate committee concluded that GSK had known about the drug’s heart risks for more than a decade without reporting them to regulators. GSK denied the charge. Sales of Avandia are currently restricted in the United States and banned in Europe.

Three Bad Luck Drugs in The Treatment of Type 2 Diabetes

Three similar diabetes drugs belonging to “thiazolidinedione” class, Troglitazone (Rezulin by Daiichi Sanyko Co.), Rosiglitazone (Avandia by GlaxoSmithKline) and Pioglitazone (Actos by Takeda Pharmaceuticals), help increase insulin sensitivity and are widely used in the treatment of type 2 diabetes.  Unfortunately, Rezulin was withdrawn from the U.S. market in 2000 due to hepatotoxicity.  Recently, Avandia was restricted for use in type 2 diabetes treatment due to increased heart attack and stroke risks.  Similarly, Actos was faced postmarket safety review of potential increased risk of bladder cancer.

Drug Effects Are Not That Easy to Study

From a biomedical scientist’s point of view, seeing those drugs crashed and burned is very frustrating.  On average, it costs ~$1.8 billion and 10- to 15-year timeframe to develop and bring a drug to market, let alone a possible withdrawal by FDA even after a drug goes on the market.  Why is it so hard to come out a safe and efficient drug?  In this case, I think the answers may lie in the undiscovered biological properties of cell membranes.  It’s been shown that small molecule’s perturbation to lipid bilayers (an essential component of cell membranes) can influence membrane proteins’ (e.g. ion channels, ion transporters, and receptors) functions.  The effects of above three famous bilayer-modifying molecules belong to “thiazolidinedione” class of drug acting as peroxisome proliferators-activated receptors gamma (PPARg) ligands that have multiple and profound effects on gene regulation, development, and metabolism.  In other words, these drugs somehow influence the cell membrane properties through complicated mechanisms, thereby causing functional changes of many unknown and unidentified targets.  In drug development world, the cost of “unknown” is very difficult to put a price tag on it.

Drug Development Business Seeks a Balancing Act Between Risks and Benefits

Again, no drug is perfect without any safety issue.  It’s a balancing act of the risks and benefits measurement and management.  When one drug flops, more will come; it is the failure we learn to make things better (hopefully)!

Until next post, keep on reading and writing!!

About fdabiomed
I like to read, organize, and write about biomedical related topics. I am passionate to learn new things, particularly news related to the Food and Drug Administration's decision and announcement, as well as the decision impacting on company's stock price.

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