Drug Combo Shows Promise for Obesity Treatment

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A combination of two drugs —  along with advice regarding healthy diet and exercise — may be an effective treatment for obesity, a new study suggests.

Participants in the study who took the drug combination lost more weight on average than those who took a placebo. Seventy percent of subjects who took a high dose of the two drugs, phentermine and topiramate, experienced a 5 percent weight loss after one year.

The weight loss  achieved from this drug combination was greater than that seen in earlier studies of patients who took orlistat, currently the only drug approved to treat obesity over the long term.

The treatment may provide another option for those who have not been able to lose weight with current therapies, said study researcher Dr. Kishore M. Gadde, director of the obesity clinical trials program at Duke University Medical Center.

"After trying diet and exercise, you have only orlistatfor long-term treatment of obesity," Gaddesaid. "And if that doesn't help you, you have to jump to surgery."

"This potentially fills the gap that exists between lifestyle changes that are treatments for obesity — diet and exercise — and surgery," Gadde said.

However, others argue patients in this study were highly selected — only a few were chosen per month out of the many that were eligible — so researchers don't know whether the general population of overweight and obese individuals could lose the same amount of weight, said Dr. Pieter Cohen, an assistant professor of medicine at Harvard Medical School and a general internist at Cambridge Health Alliance, who was not involved in the study.

In addition, patients were not studied after they stopped taking the medication, so it's not clear whether the weight loss could be maintained over the long term. Patients might have to be on the drugs for the rest of their lives, Cohen said, and the safety of such a regime is not known.

Although not common in the study, some patients on the drugs experienced serious side effects, including anxiety and depression. Side effects were worse with a higher dose of medication. There has been concern over the safety of weight loss drugs in recent years. In October, the weight loss drug Meridia was removed from the market after it was linked to an increased risk of heart attack and stroke. And in February, the Food and Drug Administration rejected approval of the weight loss drug Contrave, citing concerns with the drug's potential cardiovascular risks.

"What we need to know is will taking these medications increase or decrease the amount of strokes and heart attacks these patients will experience," Cohen said.

The study is published online today (April 11) in the journal the Lancet.

Drug combination

Phentermine is approved by the Food and Drug Administration for the short-term treatment of obesity, meaning that patients can take it for about 12 weeks. But no rigorously designed studies have looked at the drug's effects over the long term. Topiramate is a drug used to treat seizures. It has been shown to assist in weight loss in previous studies, but often causes psychiatric side effects at high doses. It was thought a combination of the drugs using lower doses might be more tolerable.

The new study involved 2,487 overweight or obese people from 93 centers in the United States. Participants were required to have at least two conditions in addition to their obesity, such as diabetes and high blood pressure.

Patients were randomly assigned to receive one of three treatments: a placebo, phentermine and topiramate, or a higher dose of phentermine and topiramate. About 1,000 patients received the placebo, 500 received the low dose and 1,000 took the high dose of the drug combination. All participants also received information on healthy diet and lifestyle practices.

After a little more than a year, participants in the placebo group lost an average of 3 pounds (1.4 kg), participants in the lower dose drug combination group lost an average of 18 pounds (8.1 kg) and those in the higher dose group lost an average of 22 pounds (10.2 kg).

Twenty-one percent of participants taking the placebo achieved a 5 percent weight loss compared with 62 percent in the lower dose drug group that achieved that weight loss and 70 percent in the higher dose drug group.

The drug combination was also able to lower blood pressure and insulin levels.

The combination may be more effective than current obesity drug treatments because the drugs have several ways they act on the body to induce weight loss.

"When you have a drug with multiple mechanisms of action, there's a greater chance that it's going to have much more efficacy," Gadde said. "The brain has the capacity to find a way to make you eat again if we are just manipulating one small pathway. If you're attacking the appetite centers from a number of different angles, you have potentially greater success."

More research needed

Future studies need to look at whether the drug combination would be more effective than aggressive lifestyle interventions, Cohen said. In this study, participants were given reading material describing healthy habits, but this type of intervention is known not to be effective, he said. Aggressive interventions, which help patients strategize about their weight loss and include meetings with nutritionists, have been shown to cause up to 10 percent weight loss, Cohen said.

Without this data, Cohen suspects it is unlikely the Food and Drug Administration would approve the drug combination for treatment of obesity, Cohen said.

"In fact, the FDA already considered the data from this trial and last year denied approval for this combination because the risks likely outweight the benefits," Cohen said, referring to the FDA decision last October, which denied approval to Qnexa, a drug that combines phentermine and topiramate. "This is a very small select group of patients, comparing medications against doing nothing at all, and that’s not the type of data that we need to decide whether a medication is going to truly make a difference in the lives of overweight and obese patients."

Pass it on: A combination of two drugs generated up to a 10 percent weight loss in obese individuals after one year. However, more research is needed to see whether the results apply to the general population and investigate the safety of the drugs.

Rachael Rettner

Rachael is a Live Science contributor, and was a former channel editor and senior writer for Live Science between 2010 and 2022. She has a master's degree in journalism from New York University's Science, Health and Environmental Reporting Program. She also holds a B.S. in molecular biology and an M.S. in biology from the University of California, San Diego. Her work has appeared in Scienceline, The Washington Post and Scientific American.