New Combination of 2 Older Drugs Helps People Lose Weight

The most common side effects the study participants experienced were dry mouth, a pins-and-needles sensation, constipation, insomnia, dizziness and a metallic taste. The study also found that patients on the higher-dose combo were at increased risk of depression (a problem affecting 7 percent of these patients) and anxiety (8 percent). This was not the case for patients on the lower dose, but the authors advise a "cautious approach" in using the drug combination for people with mood disorders.

Topiramate alone, especially at higher doses, has been associated with both depressive mood changes and memory problems. Phentermine by itself can boost blood pressure, an effect not seen with the combination.

Doses of phentermine given in the study were about a quarter to half the typical dosage, says lead author Kishore M. Gadde, M.D., of Duke University Medical Center. The highest dose of topiramate in the study was less than a quarter of what's usually prescribed for epilepsy.

In addition to the reduced dosages, the fact that the drugs work in different ways and have some opposing effects may help minimize unwanted symptoms. "Phentermine is stimulating," says Gadde, "and topiramate can cause fatigue. It's often taken in the evening or at night because it could put people to sleep, while the phentermine can cause insomnia. So some of these side effects could cancel each other out."

Earlier efforts to develop topiramate alone as a weight-loss drug were abandoned because of side effects.

Phentermine, meanwhile, is familiar to many as one-half of the 1990s weight-loss combo "fen-phen" that caused serious heart-valve abnormalities. But it was the other half of the combo, fenfluramine, that was identified as the culprit and banned in 1997. Phentermine remains the most commonly prescribed weight-loss drug today. It was approved by the FDA in 1959 as a short-term diet aid, the most common approach to obesity at the time. The current study examined its effects over a year, the longest period to date.

The study was sponsored by the drugmaker Vivus, which hopes to sell the combination in a gradual-release capsule under the brand name Qnexa. Last October the FDA rejected the company's application to market Qnexa, requesting more information establishing that it poses no risk to the heart or to the fetus in pregnancy. The company expects to file a new application by the end of the year.

The only drug currently approved as a long-term aid in weight loss, Orlistat, works by blocking fat absorption; results have not been as strong as those seen in the phentermine-topiramate study.

Katharine Greider lives in New York and writes about health and medicine.