Diabetes Drugs and Heart Risk

Sept. 11, 2007 – New studies link the oral diabetes drug Avandia -- but not the related drug Actos -- to heart attacks.

One of the studies published in The Journal of the American Medical Association is a new analysis of data from Avandia clinical trials by Wake Forest University researcher Sonal Singh, MD, and colleagues.

Using stringent criteria for data selection -- one of the study authors helped write the international guidelines for analyzing side effect data from multiple studies -- the study showed that Avandia increases a diabetes patient's risk of heart attack by 42%.

"Regulatory agencies ought to re-evaluate whether [Avandia] should be allowed to remain on the market," Singh and colleagues conclude. "Health plans and physicians should not wait for regulatory actions. They should avoid using [Avandia] in patients with diabetes who are at risk of cardiovascular events, especially since safer drugs are available."

The 42% increase in heart attack risk seen in the Singh study is nearly the same as the 43% risk found in a controversial earlier analysis led by Cleveland Clinic cardiology chairman Steven Nissen, MD. Unlike the Nissen analysis, however, the new study does not link Avandia to a higher risk of heart death.

"It is absence of evidence, not evidence of absence of an effect on mortality," Singh tells WebMD. "But at least based on this information, we cannot say Avandia increases mortality."

GSK Disputes Avandia Findings

Avandia maker GlaxoSmithKline says the Singh team's conclusions "offer no new information on the safety of Avandia." In a statement, GSK notes that the stringent criteria used in the study results in the use of data from only four studies and "reflects a difference of only 11 events in 14,291 patients" between the Avandia group and a control group.

"On this limited meta-analysis, in the context of all the other evidence, we believe it is inappropriate for the author to advise doctors to disregard the FDA’s advice -- which is to keep patients who are effectively controlling their diabetes on Avandia," the GSK statement says.

Singh says the FDA did not conduct a full risk-benefit analysis of Avandia and that its Avandia advisory panel did not evaluate the drug's full risk profile.

"The evidence confirms a significantly increased risk of heart attack with [Avandia] and a doubling in the risk of heart failure compared to other oral [blood sugar-reducing] agents," Singh tells WebMD. "We are waiting for clinical trial evidence suggesting that [Avandia] use leads to a reduction in the morbidity and mortality in patients with type 2 diabetes. Until such evidence becomes available, we stand by our statement that [Avandia] should not be used in diabetic patients at risk for cardiovascular events."

Clinical trials have not yet demonstrated a clear survival benefit or reduction in diabetes complications for patients taking Avandia. But they do show that Avandia helps people with diabetes control their blood sugar.

"We know from clinical studies that effective treatment of diabetes requires intensive, long-term, day-to-day control of blood sugar levels to reduce the risk of serious complications (such as blindness, kidney failure, limb amputation, nerve injury) and ultimately save lives," the GSK statement says. "Avandia is the most widely studied oral medication for type 2 diabetes, and is an important option for physicians who often need to prescribe several different diabetes medicines in combination to help their patients maintain blood sugar control."