Scientists believe they’ve solved the mystery of why a diabetes drug introduced in 1997 caused fatal liver failure in 63 patients.
Their discovery makes it likely that similar drug-related deaths can be prevented in the future.
In 1997, troglitazone was approved for use in the United States as one of the first drugs designed to treat type 2 diabetes. It was withdrawn from the market in 2000 after 63 people died from liver failure after taking it.
No one at the time really understood what happened. In preclinical studies using rats, there was no sign of danger to the liver. During human trials, adverse effects from the drug were characterized as rare and relatively mild. There were some hints at the potential for liver damage, but they weren’t enough to prevent approval by the Food and Drug Administration.
“Rats didn’t have a problem handling the drug, and the human trials weren’t large enough for the true risk of liver injury to become apparent,” says Paul Watkins, coauthor of the study and professor of medicine and pharmacy at University of North Carolina. He is the director of the Hamner-UNC Institute for Drug Safety Sciences.
“Once the drug was given to a larger population that contained patients unable to properly process the drug, people started to turn yellow and die of liver failure.”