SUNDAY, April 10 (HealthDay News) -- Obese patients taking a high dose of an investigational weight-loss pill called Qnexa lost an average of 22 pounds over a year, while also lowering their cholesterol and blood pressure numbers, a new study has found.
Qnexa is a combination of two medications: phentermine, the most widely used weight-loss drug in the United States, currently available under a variety of brand names as well as a generic; and topiramate (Topamax), best known as a drug used to ease epilepsy and migraine.
Qnexa was recently turned down as a weight-loss aid by the U.S. Food and Drug Administration, because there was not enough data on the risk of birth defects and heart problems related to the drug. Topiramate has been linked to an increased risk for cleft lip/palate in babies born to women who took the drug.
The results of the new study, which was funded by Vivus, Qnexa's maker, suggest that "the combination of topiramate and phentermine when administered with some lifestyle counseling could be a valuable treatment for obesity," said lead researcher Dr. Kishore Gadde, an assistant professor of psychiatry and director of the obesity clinical trials program at Duke University Medical Center.
One reason for the significant weight-loss is that these drugs work by different mechanisms, Gadde said. "In a treatment, [with] the more mechanisms you have there is a greater likelihood of achieving the kind of weight loss we are hoping for, in a large proportion of patients," he said.
In addition, the combination of drugs may alter the side effect profile for each drug, he speculated. "The thinking behind the combination of the drugs is that some of the side effects could actually cancel out," Gadde said. "Topiramate causes fatigue, and phentermine is a stimulant, so they could be negating the side effects of each other."
Topiramate can also cause mood changes, while phentermine is more uplifting, he added.
The report is published in the April 11 online edition of The Lancet.
In this multicenter trial, called CONQUER, Gadde's team randomly assigned almost 2,500 overweight and obese men and women to diet and exercise counseling alone or to counseling alongside once-daily low- or high-dose Qnexa in pill form. Low-dose Qnexa contained 7.5 milligrams (mg) of phentermine and 46 mg topiramate, while the high-dose pill contained 15 mg of phentermine and 92 mg of topiramate.
After 56 weeks, patients on either dose of Qnexa had lost significantly more weight than those who only took part in the counseling program, the researchers found.
Those not taking the combo drug had an average weight-loss of 3 pounds, compared with 18 pounds for those on low-dose Qnexa and 22 pounds for those on the high-dose Qnexa.
Moreover, while 21 percent of those in the counseling program alone lost at least 5 percent of their weight, that number rose to 62 percent of those on low-dose Qnexa and 70 percent for those on the high-dose regimen.
In addition, people taking Qnexa saw reductions in their blood pressure, blood cholesterol levels, triglycerides (a blood fat) and blood sugar levels, Gadde's group found.
The ideal candidates for this treatment are obese and overweight people whose weight is affecting their health, Gadde said.
"When you are looking for weight-loss in patients, it shouldn't be for cosmetic reasons," he said. "An ideal candidate for weight-loss is someone that has obesity-related [health] risks."
Gadde noted that the weight-loss seen in the first year of the trial was maintained in the second year of the trial.
Side effects did occur in some patients, and were especially common at the higher dose. In those taking high-dose Qnexa, the most common side effects were dry mouth (21 percent), paresthesia, or a feeling of "pins and needles" (21 percent), constipation (17 percent), insomnia, dizziness and distorted taste (10 percent each).
Paresthesia is a common side effect of phentermine, Gadde noted, while the other side effects are most likely associated with topiramate.
An increased risk of depression and anxiety was also noted in those taking the drugs, seeming to increase as the dosage given rose. About twice the number of people in the high-dose drug groups dropped out of the trial compared to people receiving counseling alone, the researchers noted.
"If you see side effects like depression and anxiety, you need to be more careful," Gadde said. "You don't give these drugs to someone who is clinically depressed," he added.
According to Gadde, there were no birth defects among any of the babies born to the 34 women who became pregnant while taking Qnexa in this trial.
Ashley Buford, a spokeswoman for Vivus, said the company is hoping to resubmit its application for approval of Qnexa to the FDA by the end of the year.
Commenting on the study, obesity expert Dr. David L. Katz, director of the Prevention Research Center at Yale University School of Medicine, said that "this study shows what we had cause to believe before: that Qnexa facilitates weight loss beyond office-based counseling alone, as long as people are taking the drug."
However, the weight loss may be unlikely to persist if use of the drug stops, he said.
"In addition, we don't yet know if Qnexa is safe for long-term, or even lifelong use, and thus cannot yet say whether it is safe and useful for long-term weight control," Katz said. "Other drugs that have facilitated weight loss in the short term have failed to translate to safe and effective long-term use. This is the bar a truly useful weight-loss drug will need to clear," he said.
For more on obesity, visit the U.S. National Library of Medicine.
SOURCES: Kishore Gadde, M.D., assistant professor, psychiatry, director, obesity clinical trials program, Duke University Medical Center, Durham, N.C.; David L. Katz, M.D., M.P.H., director, Prevention Research Center, Yale University School of Medicine, New Haven, Conn.; April 10, 2011, The Lancet, online
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