Avandia, Other Aggressive Diabetes Treatments, Linked to DeathsJun 9, 2008 | Parker Waichman LLP According to researchers comparing the results of two diabetes trials, weight gain, the use of multiple drug combinations, and even lowering blood sugar too low, too fast may have been factors in causing early deaths. Both trials, one conducted in the United States and Canada, the other in Australia, were designed to measure the benefits of using drugs such as Avandia to dramatically lower blood sugar in diabetes patients.
The two trials followed over 21,000 elderly, often obese, diabetics, using multiple drugs—including Avandia—to tightly control blood sugar levels in an effort to avoid complications that can cause disability and death. While cutting kidney disease in one trial, the treatments—which included Avandia—failed to protect diabetics from heart disease and stroke in the second. Avandia was given to 90 percent of the intensive therapy group in the second—Accord—trial. Both studies, the largest ever for diabetes, were just published by the New England Journal of Medicine.
The conflicted findings call into question the common use of powerful drug combinations to slash the blood sugar of diabetics to levels seen in non-diabetics, said Harlan Krumholz, a Yale University cardiologist not involved in the studies. "The results are surprising and question the conventional wisdom that the lower you get blood sugar, the better off patients are and the lower their risk," Krumholz said. "These studies should give us pause" about the current standard of treatment.
The most frequently used drug in the two trials was GlaxoSmithKline's Avandia, which was linked to increased risk of heart attacks in findings released last May.
In April, the Food & Drug Administration (FDA) issued a warning to GlaxoSmithKline for not reporting safety results on Avandia saying that between 2001 and 2007 GlaxoSmithKline neglected to update the agency on over 10 ongoing studies of Avandia, as required by regulations. The FDA acknowledges that information from those studies was included and disclosed in other notices to the government; however, the FDA categorizes the omissions as “serious,” saying that the omissions “may be symptomatic of underlying post-market reporting failures.” Last November, Avandia received a Black Box warning, which is the most serious labeling warning that a drug can carry. The labeling change to the Black Box followed several high-profile congressional hearings where the FDA and Glaxo were criticized for not disclosing the drug’s potential risks earlier.
The US trial, called Accord, was stopped in February when researchers found patients were more likely to die with aggressive treatment, which included the controversial diabetes medicine, Avandia. Conversely, Advance—the Australian trial—indicated treatment reduced the risk of kidney disease by one-fifth without increasing risk of death. "These findings reinforce that blood glucose lowering in diabetes is safe and has an important role to play in the prevention of serious complications," said Dr. Anushka Patel of the University of Sydney, who presented the findings at the American Diabetes Association meeting in San Francisco. Details of both trials were also released online in the New England Journal of Medicine on Friday.