Rosiglitazone
Rosiglitazone (trade name Avandia) is an antidiabetic drug in the thiazolidinedione class. It works as an insulin sensitizer, by binding to the PPAR in fat cells and making the cells more responsive to insulin. It is marketed by the pharmaceutical company GlaxoSmithKline (GSK) as a stand-alone drug or for use in combination with metformin or with glimepiride. First released in 1999, annual sales peaked at approximately $2.5-billion in 2006; however, following a meta-analysis in 2007 that linked the drug's use to an increased risk of heart attack, sales plummeted to just $9.5-million in 2012. The drug's patent expired in 2012.
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| Trade names | Avandia |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a699023 |
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| Routes of administration | By mouth |
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| Bioavailability | 99% |
| Protein binding | 99.8% |
| Metabolism | Liver (CYP2C8-mediated) |
| Elimination half-life | 3–4 hours |
| Excretion | Kidney (64%) and fecal (23%) |
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| ECHA InfoCard | 100.108.114 |
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| Formula | C18H19N3O3S |
| Molar mass | 357.43 g·mol−1 |
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| Chirality | Racemic mixture |
| Melting point | 122 to 123 °C (252 to 253 °F) |
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It was patented in 1987 and approved for medical use in 1999. Despite rosiglitazone's effectiveness at decreasing blood sugar in type 2 diabetes mellitus, its use decreased dramatically as studies showed apparent associations with increased risks of heart attacks and death. Adverse effects alleged to be caused by rosiglitazone were the subject of over 13,000 lawsuits against GSK; as of July 2010, GSK had agreed to settlements on more than 11,500 of these suits.
Some reviewers recommended rosiglitazone be taken off the market, but an FDA panel disagreed, and it remains available in the U.S. From November 2011 until November 2013, the federal government did not allow Avandia to be sold without a prescription from a certified doctor; moreover, patients were required to be informed of the risks associated with its use, and the drug had to be purchased by mail order through specified pharmacies. In 2013, the FDA lifted its earlier restrictions on rosiglitazone after reviewing the results of a 2009 trial which failed to show increased heart attack risk.
In Europe, the European Medicines Agency (EMA) recommended in September 2010 that the drug be suspended because the benefits no longer outweighed the risks. It was withdrawn from the market in the UK, Spain and India in 2010, and in New Zealand and South Africa in 2011.