The widely used diabetes drug Avandia increases the chance of serious heart problems, including a 30% to 40% higher risk of myocardial ischemia, or decreased flow of blood to the heart, according to documents released by the Food and Drug Administration on Thursday.
Diabetics taking the GlaxoSmithKline drug in combination with insulin were at even greater risk, the FDA found in a review of dozens of drug studies.
The analysis also found hints that pre-diabetics taking Avandia with ACE inhibitors, a class of heart drugs used for lowering blood pressure, faced a higher risk of myocardial ischemia.
FDA's division of drug risk evaluation concluded that the agency should issue the strongest available warning about the risk of myocardial ischemia in people who use Avandia, the documents showed.
The proposed "black box" warning would state that patients with heart disease or who are taking insulin should not use the drug.
Actos, or pioglitazone, a drug manufactured by Takeda Pharmaceutical Co. and in the same class as Avandia, carried no similar risks, according to the FDA analysis.
The documents were released in advance of an FDA advisory panel meeting on Monday to review the drug's safety. The panel could recommend stronger warnings or withdraw the drug from the market. The FDA isn't required to follow the advice of its outside experts but typically does.
In May, a study in the New England Journal of Medicine linked Avandia to a 43% increase in the risk of heart attacks. The study was led by Dr. Steven Nissen, a cardiologist at the Cleveland Clinic in Ohio and a nonvoting member of the FDA panel.
After publication of that study, the FDA issued an alert reassuring patients that it had two studies that showed Avandia was safe.
But in the newly released documents, Dr. David Graham, a safety reviewer, said one of the studies was unreliable and could not be used to resolve safety concerns.
Used daily by nearly a million Americans with Type 2 diabetes to control blood sugar, Avandia had sales of $3.4 billion in 2006. However, sales have slumped 20% since May and could further drop if the panel recommends additional warnings.
Dr. Anne Phillips, vice president of clinical development at GlaxoSmithKline, said company studies of 400,000 patients showed "no increase in cardiovascular mortality, no increased risk of myocardial infarctions [heart attacks] and no increase in mortality from all causes."
The findings were not available to FDA staffers when they prepared the documents released Thursday, she said.