麻豆传媒

Even though there are scant data, obesity researchers and patients have already put a name to a potential new weight-loss craze: Belphen, a combination of lorcaserin (Belviq) and phentermine.

The name is a play on , the wildly popular diet drug that helped patients shed pounds in the 1990s, but at the expense of heart valve problems.

When it was pulled from the market in 1997, the fenfluramine (or dexfenfluramine) half was suspected of being the driver of the cardiac problems, not the phentermine half.

Belviq was approved by the FDA in 2012. While fenfluramine targeted serotonin 5-HT2B receptors, which are abundant in the heart, Belviq works on 5-HT2C receptors, which aren't found there.

Trials of Belviq -- the drug brought in $5.7 million for its makers in 2013 -- didn't turn up any significant sign of heart valve or other major cardiovascular issues in phase III studies.

But will doctors prescribe Belviq paired with phentermine -- a combination not sanctioned by the FDA -- when patients start demanding it?

Physicians who spoke with 麻豆传媒 said they'll wait for the results of a and sponsored by Eisai, which markets Belviq with Arena Pharmaceuticals.

It's a safety study of 225 patients with a primary outcome of serotonergic adverse events including headache, dizziness, nausea, fatigue, dry mouth, diarrhea, vomiting, insomnia, or anxiety.

Efficacy is a secondary endpoint, with outcome measures of weight loss, waist circumference changes, and other metabolic parameters.

Patients will take the usual dose of Belviq (10 mg twice a day) plus 15 mg of phentermine either once or twice a day.

However, there's no placebo group, and the study won't include echocardiograms because cardiovascular safety was established in earlier studies of Belviq, and is also ongoing in dedicated trials, according to , of the Pennington Biomedical Research Center in Baton Rouge, La., one of the study sites for the Belphen trial.

"They did so many echos in phase III trials and didn't see a significant difference," Greenway said, "so that doesn't seem to be important."

, of Weill Cornell Medical College in New York City, who is the principal investigator for the trial at that site, agreed that echo data would be unnecessary.

"With Fen-Phen, there was no evidence that phentermine did anything at all," Aronne said. "It didn't cause valvular heart disease and it didn't contribute to valvular heart disease."

, professor emeritus of Pennington Biomedical Research Center who is not involved in the study, said she "would not prescribe this combination until the trial is published. The trial is large enough to give us an idea of safety."

She agreed that the echocardiogram studies done in about 3,500 patients in the phase III trials of Belviq bolster confidence that the drug won't lead to heart valve problems. But she added that a "very low risk of valvulopathy cannot be excluded with certainty without a much larger study."

, of Massachusetts General Hospital in Boston, said he wouldn't feel comfortable prescribing Belphen because the safety studies haven't been done.

And , of Yale University Prevention Research Center, said the long-term safety of both drugs remains "unconvincing."

"This ... looks a lot like an opportunity to repeat the dangerous follies of history," Katz told 麻豆传媒.

But Aronne pointed out that there are so few options to treat obesity.

"In hypertension, we have over 100 medications in 10 different therapeutic categories," he said. "In obesity, we have just a few drugs and a far more complex system. There's a natural tendency to take what's available and use it because of the difficulties in treating obesity."

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