A weight-loss pill taken by millions of patients over the past two decades has been underpinned by problematic clinical studies “systematically underestimated” the potential harms of the drug, according to a new analysis . Danish researchers who reviewed data and summaries of articles published journals found that seven drug trials funded by drug maker Roche in the 1990s downplayed the apparent frequency of side effects such as diarrhea and incontinence.
The drug, known by scientists as orlistat, and marketed in the US as Alli, it has generated hundreds of millions of dollars in sales, but has fallen in recent years, partly due to the reputation of unpleasant gastrointestinal side effects.
The analysis sheds light on “something doctors are often suspected: that the reporting of adverse events in clinical trials does not give the full picture,” said Dr. Raj Padwal, a clinical pharmacologist and internist at the University of Alberta, who was not involved in the analysis.
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The new research, published Tuesday in the journal PLoS Medicine, did not examine the data reports that were submitted to the Food and Drug Administration when it was approved orlistat, for the first time in 1999 as a prescription drug sold by Roche as xenical or later as a low dose, over-the-counter pills sold by GlaxoSmithKline as Alli . (The FDA, however, review data from the trials in question.)
These trials, conducted in the 1990s by researchers in academic or medical centers, resulted in magazine articles. To assess the thoroughness of these articles, the Danish researchers compared them with summaries of the data submitted to European regulators, which were obtained by submitting requests Freedom of Information Act. They found that the publications disclose only a fraction – between 14 and 33 percent -. Called “adverse events” of patients compared with data summaries
for example, two publications are out apparent side effects occurred in less than 5 percent of trial participants; others counted several reports of the same patient just an adverse event.
Two other articles currently listed on the website of Alli as evidence of safety and efficacy of the drug, were also problematic. One only apparent side effects were reported considered “common”; the other reports omitted from apparent side effects that were not at least twice as common among trial participants taking the drug and those taking a placebo.
All the studies in question are still standing in the scientific literature.
Anja von Treskow, a spokeswoman for Roche, said reporting on trials “was performed according to the standards of the time” and that the company “continually update [s] our methods” meet changing standards.
Joanmarie Goddard, a spokeswoman marketer Alli, GlaxoSmithKline, said the company “take [s] adverse event reports for our products very seriously and routinely monitor [s] security information together with health professionals and regulatory agencies worldwide. ”
The rise and fall of a weight loss pill
In the first year after Roche Xenical brought to market in the US, the drug brought $ 600 million people worldwide. Throughout the 2000s, the drug was prescribed 11 million times in the US, according to an analysis of data on the consumer group Public Citizen. When GSK launched the drug counter as Alli in 2007, which blew through the doors, selling $ 155 million in their first weeks on the market.
The drug, which is intended to be paired with diet and exercise, works by preventing the body from absorbing fat. But excrete high fat makes oily stool, resulting in gastrointestinal side effects for many patients.
Even at the peak of the drug, warning signs they were evident. US prescriptions for Xenical decreased each year. A 2007 study almost 17,000 patients found that only 6 percent of the participants were still taking Xenical after one year; after two years, it was reduced to 2 percent.
This is an indication that “the balance between effectiveness and adverse effects is not very beneficial,” said Dr. Jeppe Schroll, lead author of the new analysis and a researcher at the Nordic Cochrane Centre in Copenhagen.
Then in 2010, the FDA added a warning to both Xenical and Alli warning about the “rare” reports of liver damage; A study 2012 found alarming effects of toxicity such that the investigator immediately reported its findings to the FDA.
Roche no longer sold in the US Xenical, although generic versions of prescription drugs are still available. GSK no longer breaks out sales of Alli in its financial reports, and did not comment on current sales figures of the drug. A package of 120 pills Alli sold online for $ 56.
Despite the struggles of orlistat, drug manufacturers are not giving up taking the pill. A Canadian pharmaceutical company, pharmaceutical M is working in a reformulated alternative to stay away from the existing “socially unacceptable” underwear drug issues. ”
The problem of hidden damage
is difficult to say how common the damage reported discrepancies discovered in the new analysis are orlistat.
The Danish researchers found that space restrictions in magazines may have played a role in what is disclosed, and that the rules for submission of data that have already been developed could make results less applicable to new drugs.
Dr. Rohan Khera, a fellow cardiology at UT Southwestern Medical Center, who has studied the effectiveness of different drugs to lose weight, called the new analysis “a good start to find out that there is a need to study this in more detail . “
Dr. Sidney Wolfe, consumer advocate Public Citizen has unsuccessful requested US regulators to take orlistat off the market, believes that the stakes are high. “If you are a doctor and rely on medical journals, can be fooled. Doctors do not have time to go read the actual raw data,” he said.