Diet pill Meridia may garner new warning labels or be pulled from the market completely following today's meeting of the Food and Drug Administration's drug advisory committee.
In a vote this afternoon on the safety of the Abbott Laboratories' diet drug, panel members were split -- eight voted to boot the drug from the market while the remaining eight voted to keep it on the market with new safety restrictions.
Spurred by concern that Meridia might increase cardiovascular risk, Abbott Laboratories had sponsored a six-year trial, SCOUT, to further evaluate its safety, the results of which were reviewed today by the committee.
Now that results are in, it will be up to the FDA to consider the split decision and weigh whether the 16 percent increased risk in major adverse cardiac events seen in the trial is reason enough to restrict access or withdraw the drug from the U.S. market.
Given that patients on Meridia only lost five pounds more in the study than those on placebo, many doctors feel that this increased cardiovascular risk is simply not worth it.
"The key point here is that obesity itself is associated with increased risk of cardiovascular disease, so the rationale for prescribing obesity drugs is to improve outcomes [by lowering that risk]," says Dr. Kevin Niswender, assistant professor of medicine at the Vanderbilt University School of Medicine.
"A drug that is modestly successful at increasing weight loss but increases cardiac risk further, that's clearly an issue," he said.
Abbot Laboratories products containing Meridia's main ingredient, Sibutramine, were already pulled from the European market in January based on preliminary results from SCOUT.
SCOUT Study Finds Faults
SCOUT is a double blind placebo-controlled study that tested a 10 mg dose of Meridia plus diet and exercise in about 5,000 patients, comparing their side effects and weight loss to 5,000 control patients who followed diet and exercise and received a placebo pill.
Subjects were those with cardiovascular disease or type 2 diabetes who had not had a heart attack or stroke in the previous three months before starting the trial.
Though Abbot Laboratories expected its drug to decrease cardiovascular risk at the onset of the trial, the outcome six years down the road veered in the other direction.
"The SCOUT trial was powered on the assumption that sibutramine-related weight loss would reduce the relative risk for [major adverse cardiac events] by at least 15 percent. In contrast to this expected outcome, in an intent-to-treat analysis, the hazard ratio for [major adverse cardiac events] was 16 percent higher in subjects treated with sibutramine versus placebo," clinical reviewer of the trial, Dr. Monique Falconer, writes in the FDA briefing material on the drug.
What's more, it is possible that the study design may have underestimated the cardiac risks.
All subjects in the study underwent a six-week trial of the drug before starting the study. Some 900 subjects who had an immediate negative reaction to the drug, such as an increase in blood pressure or pulse rate, were thrown out of the study. The remaining subjects were randomized and used in the trial.
"If you kick out the 940 worst patients in terms of adverse drug responses, then still have worse outcomes on the drug, imagine how bad it would have been if you included the dropouts. This is fake research, and sadly typical for company-sponsored studies," said Dr. John Pippin, senior medical and research adviser for the Physicians Committee for Responsible Medicine.
A Safe Way for Meridia?
Conversely, the fact that all subjects were already at increased cardiovascular risk by virtue of the fact that the study selected for this trait, some might argue that the increased risk could be avoided if doctors prescribed the diet drug only to patients who are in good cardiovascular health.
"Those receiving treatment in the study are a homogenous population," Niswender said. "But as physicians we tailor therapies to patients."
Though only a minority of obese patients does not suffer from increased cardiovascular risk, Niswender said it is possible these patients could benefit from the drug without seeing undo increase in risk.
However, some preliminary data show an increase in adverse cardiac events, even in those in good cardiovascular health, Pippin said.
Given the small effect on weight seen in trials, he said approving a drug with so little therapeutic effect but a persistent cardiac effect is "crazy."
Diet Drugs and Heart Health Effects
Meridia's potential to increase heart rate and blood pressure was known at the time of its FDA approval for weight loss back in 1997.
Since then, the company has added warnings concerning the drug, noting that those ever suffering from heart attack, heart arrhythmia, stroke, arterial disease, or uncontrolled high blood pressure should not be on the drug.
Meridia's effect on weight loss and its effect on heart health are indelibly tied, Pippin said.
"When we eat, our brain releases neurochemicals that tell us we're full, the most prominent of which is serotonin. Meridia and certain other diet drugs, they block the action that makes that serotonin go away, giving you the feeling that you are full continually, which makes you eat less," he said.
Unfortunately, the excess presence of these chemicals has potentially negative effects on the cardiovascular system as well, he said, which is why a number of diet drugs that work in this way have ended up causing heart problems in some patients.
A prominent example of this is fen-phen, a popular diet drug of the 1990s. Fenfluramine, a main ingredient in the pill, was found to be associated with valvular heart disease and pulled from the market in 1997.
More recently, Arena Pharmaceuticals has been developing a diet drug thought to use the same pathway as fen-phen but in supposedly safer way. The FDA released a statement Tuesday however, which called out the safety of the new drug, noting issues with heart valve disease and psychiatric side effects with its main ingredient, lorcaserin.
"I think the FDA has been burned with cardiovascular disease for a number of diet drugs that have been on the market," Niswender said. "I think this is part of their rationale for requiring more stringent cardiovascular data up front for diabetes drugs. It's going to take more [in the future] to get these drugs approved."
ABC News' Kim Carollo contributed on this report.