Steven Nissen (b. 1948)
In 1999, Avandia and Actos were welcomed in the treatment of type 2 diabetes, by far the most common form of diabetes. Members of the glitazone class of oral antidiabetic drugs, Avandia and Actos work by increasing tissue sensitivity to insulin. Rezulin, the first member of the glitazone team, was effective but permanently benched in 2000 because it caused liver toxicity that was associated with several hundred deaths.
Avandia was aggressively marketed, becoming the best-selling drug for type 2 diabetes with sales of $3.2 billion in its high-water year of 2006. However, periodically over the years, in reports repeatedly dismissed by its manufacturer SmithKline Beecham (now GlaxoSmithKline, GSK), Avandia (rosiglitazone) use was linked to an increased risk of heart attack. However, these reports attracted national attention in 2007, when an article appeared in the prestigious New England Journal of Medicine. Cleveland Clinic cardiologist Steven Nissen provided evidence from GSK and Food and Drug Administration databases that Avandia increased the risk of heart attack and other cardiovascular problems by 43 percent. Avandia remained on the market but with additional warnings displayed on its label.
In 2010, uncovered documents revealed that GSK had withheld data and concealed information regarding concerns that Avandia caused heart problems. In fact, GSK had conducted a secret trial in 1999 comparing Avandia and Actos in terms of cardiovascular risks. Avandia fared poorly, and the results were never made public.
Most published independent studies in recent years have associated Avandia use to cardiovascular problems, and in September 2010, European and American drug regulators took action. The European Medicines Agency removed Avandia from the European market. In the United States, the drug will only be available to patients if their physicians attest that every other antidiabetic drug has been tried and that the patient is aware of its potential heart risks. Actos, marketed by the Japanese pharmaceutical company Takeda, does not appear to have heart or liver toxicity risks and remains the only unrestricted glitazone.
SEE ALSO Food and Drug Administration (1906), Insulin (1921), Orinase (1957), Glucophage (1958), Human Insulin (1982).
Diabetes is the leading cause of blindness in adults age 20 to 74. The three major eye problems experienced by the diabetic are glaucoma, retinopathy, and cataracts (shown here), which are associated with elevated blood-glucose levels. The results of some recent studies suggest that Avandia, while lowering blood glucose levels, may actually increase the risk of cataract development.