Weight gain
Both thiazolidinediones cause a similar degree of weight gain to that caused by sulfonylureas (moderate strength of evidence). Eye damage
Both rosiglitazone and pioglitazone have been suspected of causing macular edema, which damages the retina of the eye and causes partial blindness. Blindness is also a possible effect of diabetes, which rosiglitazone is intended to treat. One report documented several occurrences and recommended discontinuation at the first sign of vision problems. A retrospective cohort study showed an association between the use of thiazolidinediones and the incidence of diabetic macular edema (DME). Both use was associated with a 2,3 higher risk at 1 year and at 10 year follow-up, rising to 3 if associated with insulin. Hepatotoxicity
Moderate to severe acute hepatitis has occurred in several adults who had been taking the drug at the recommended dose for two to four weeks. Plasma rosiglitazone concentrations may be increased in people with existing liver problems. Contraindications
Both rosiglitazone and pioglitazone are contraindicated in people with NYHA Class III and IV heart failure. They are not recommended for use in heart failure.In Europe rosiglitazone was contraindicated for heart failure or history of heart failure with regard to all NYHA stages, for combined use with insulin and for acute coronary syndrome. The European Medicines Agency recommended on 23 September 2010 that Avandia be suspended from the European market. Pharmacology
Rosiglitazone is a member of the thiazolidinedione class of drugs. Thiazolidinediones act as insulin sensitizers. They reduce glucose, fatty acid, and insulin blood concentrations. They work by binding to the peroxisome proliferator-activated receptors (PPARs).
Controversy and response
Following the reports in 2007 that Avandia can significantly increase the risk of heart attacks, the drug has been controversial. A 2010 article in Time uses the Avandia case as evidence of a broken FDA regulatory system that "may prove criminal as well as fatal". It details the disclosure failures, adding, "Congressional reports revealed that GSK sat on early evidence of the heart risks of its drug, and that the FDA knew of the dangers months before it informed the public." It reports, "the FDA is investigating whether GSK broke the law by failing to fully inform the agency of Avandias heart risks", according to deputy FDA commissioner Dr. Joshua Sharfstein. GSK threatened academics who reported adverse research results, and received multiple warning letters from the FDA for deceptive marketing and failure to report clinical data. The maker of the drug, GlaxoSmithKline, has dealt with serious backlash against the company for the drugs controversy. Sales on the drug dropped significantly after the story first broke in 2007, dropping from $2.5 billion in 2006 to less than $408 million in 2009 in the US.In response to the rise in risk of heart attacks, the Indian government ordered GSK to suspend its research study, called TIDE, in 2010.