Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Annual sales approx $2.5bn. Patent expires 2012.

Recent findings suggest that Rosiglitazone is associated with a statistically significant risk of myocardial ischemic events.^[1][2]

Pharmacology

Like other thiazolidinediones (TZDs), the mechanism of action of rosiglitazone is through activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPAR?. Rosiglitazone is a selective ligand of PPAR?, and has no PPAR?-binding action.

Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NF?B) levels fall and inhibitor (I?B) levels increase in patients on rosiglitazone.^[3]

Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele.^[4] This is the subject of a clinical trial currently underway.

The medication might also be effective in the treatment of mild to moderate Ulcerative Colitis, due to its antiinflammatory properties as a PPAR ligand.^[5]

Side-effects and contraindications

A press release by GlaxoSmithKline in February 2007 noted that there is a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide.^[6] The information was based on data from the ADOPT trial.^[7] The same increase has been found with pioglitazone (Actos), another TZD.

An article by Dr. Steven Nissen and his colleague Kathy Wolski in the June 14, 2007 issue of The New England Journal of Medicine reported that the use of rosiglitazone was associated with a significantly increased risk of heart attack (43% more likely, odds ratio=1.43). and an even higher risk of death from all cardiovascular diseases, (64% more likely, odds ratio=1.64).^[1][8] The FDA issued an alert on May 21 2007.^[9]

On July 30, 2007 an Advisory Committee of the Food and Drug Administration concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of myocardial ischemic events (including heart attacks) than a placebo, but data from several long term, prospective clinical trials showed than when rosiglitazone was compared to metformin, or sulfonylurea, there was no difference in the risk of heart attack. This data, coupled with the meta-analysis, prompted the FDA to state that the data on the association between rosiglitazone and myocardial ischemia were inconclusive. As early as September, 2005, both Rosiglitazone and Pioglitazone have been suspected of causing Macular Edema, which causes partial blindless in various spots of the angle of vision. While blindness is also a possible effect of diabetes, which Rosiglitazone is intended to treat, an article in Canadian journal CMAJ has documented several occurrences and recommends discontinuation at the first sign of vision problems. Both TZD's are contraindicated in patients with NYHA Class III and IV heart failure.

References

External links

• Official website
• MedlinePlus article
• Medscape

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