A Silver Bullet for Weight Loss? Maybe

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Darren Robb

If there’s one certainty about weight loss, it’s that there is no magic pill that can melt off your excess pounds.

At least, not yet. But scientists led by Dr. Kishore Gadde at Duke University report online in the journal Lancet on Sunday that a combination drug helped obese patients lose nearly 10% of their body weight in a year.

The study involved a new combination of two existing drugs: phentermine, a prescription short-term weight-loss drug, and topiramate, an anti-epilepsy medication that also leads to weight loss. The 2,487 study participants were all either overweight or obese, with a BMI of 27 to 45 (a BMI of 18.5 to 24.9 is considered normal weight). The volunteers also had at least two other conditions related to their obesity, including high blood pressure, high cholesterol or diabetes.

The participants were given standard diet and exercise counseling, and were randomly assigned to take either a once daily placebo or one of two doses of the combination weight-loss pills. The group that took the combination medication for a year lost an average of 19 lbs. more than those on placebo, and showed improvements in blood pressure, cholesterol and markers of inflammation, all of which are linked to chronic conditions such as heart disease and diabetes.

Currently, there is only one drug approved by the Food and Drug Administration (FDA) for long-term weight loss: orlistat, which is sold in prescription form as Xenical or over the counter as Alli, works by blocking absorption of fat in the gut, but doesn’t affect appetite.

By contrast, phentermine, a distant cousin of amphetamines, does decrease appetite, but it is often used only for short-term weight loss, since it’s not clear how safe or effective the stimulant might be when used over the long term. Topiramate has been tested as a weight-loss drug after epilepsy studies showed users lost weight, but its side effects of memory loss, cognitive changes and some psychiatric abnormalities hasn’t made it a popular candidate for a weight-loss treatment.

So Gadde and his group decided to look at lower doses of each of the drugs and use them in combination to boost their ability to help patients shed pounds. “If you have a treatment with multiple mechanisms, you have a greater chance of helping people to lose weight,” he says.

The team tested two different doses of the combination pill, and found that both led to more weight loss than a placebo. To consider a weight-loss pill for approval, the FDA looks for at least a 5% reduction in weight over a year; in the new study, 62% of those in the group that got the lower of the two doses of the combination pill achieved this level of weight loss compared with 21% of those in the control group. That’s important, says Gadde, since even a 5% to 10% weight loss in diabetics can lead to significant improvements in their blood sugar, blood pressure and cholesterol levels.

The group that got the higher-dose pill had even greater weight loss, but also reported more side effects — including dry mouth, numbness or tingling, constipation, insomnia, depression and anxiety — which, while mild, were still concerning. The current trial showed that the side effects disappeared after participants stopped the medication, but there may be more permanent effects to consider.

Last fall, the FDA rejected the phentermine-topiramate combination for approval, after its maker Vivus had first submitted the drug, which it calls Qnexa; the FDA asked the company for further safety studies, especially on the risk of heart problems and birth defects. Topiramate has been linked to an increased risk of cleft lip and palate deformities in babies born to women using the medication, but Gadde says that while some of the volunteers in the current study — funded by Vivus — did get pregnant during the trial, none had babies affected by this birth defect.

Still, additional trials will need to confirm both the safety and the dose of phentermine-topiramate that will provide the most weight-loss benefit with the least risk of side effects. Having an effective drug for weight loss over the long term may be an important weapon in the war on obesity, says Gadde, since it could help jump start weight reduction in the morbidly obese — enough to allow them to begin a diet and exercise program that can help them sustain weight loss. Shedding the pounds is also a powerful way to combat other chronic diseases associated with extra weight such as hypertension, heart disease and diabetes.

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