CINDY SANDERS

To the chagrin of most of us, there simply isn’t much hope of keeping the pounds away while overindulging in our favorite fatty foods. This fact is driven home to millions of Americans each January as they make the hesitant trek back to the bathroom scale to check out the damage in the wake of the holiday feasting season.

While there is no ‘magic bullet,’ researchers continue to increase their knowledge base of the body’s triggers and reactions to hunger and weight gain. The results are a number of new drug therapies in the pipeline that could be used in combination with surgery, diet and/or exercise to maximize an individual’s ability to return to a healthier weight.

Frank Greenway, MD, director of the Outpatient Research Clinic at Pennington Center, which is affiliated with Louisiana State University, said the fall scientific meeting of The Obesity Society included interesting sessions on three new drugs or drug combinations that have just wrapped up Phase III clinical trials.

“Lorcaserin is a serotonin 2C agonist,” he said of the first. “The second is a combination therapy. It’s a combination of bupropion, a sustained release preparation, and naltrexone. In combination, it’s called Contrave.” Greenway continued, “The third is Qnexa. It is a combination of topiramate and phentermine in low doses, and those are in a sustained release preparation.”

Greenway, who sits on the Clinical Council of The Obesity Society, noted all three seem to have met the Food & Drug Administration’s criteria for efficacy. Of the three, Lorcaserin seemed to have the least efficacy in terms of net weight loss in comparison to a placebo in trials.

“In efficacy, it was about halfway between orlistat and sibutramine, which are the two drugs currently approved,” noted Greenway. Orlistat typically results in about 2.9 percent of body weight lost in excess of the placebo group, lorcaserin in a 3.6 percent loss and sibutramine at about 4.5 percent. Greenway added Contrave seems to have about a 5 percent weight loss result, and Qnexa is the most effective at about 9.5 percent.

“These drugs are a step forward, but as you can tell … if 20 percent overweight is where you start, and they give between 3 and 10 percent weight loss, they are not a magic bullet,” said Greenway. “But,” he added, “they are certainly better than what we’ve had, and presumably some of them can be combined and that will give us more options.”

One of those combination possibilities is lorcaserin and phentermine. Lorcaserin is similar to the old drug fenfluramine that was taken off the market in a very public manner several years ago. While the goal of both lorcaserin and fenfluramine was to impact the serotonin 2C receptor, fenfluramine also targeted the 2B receptor. In humans, the 2B receptor is tied to heart valve metabolism, and fenfluramine was found to cause heart valve damage in some patients who took the combo drug fen-phen.

“Lorcaserin has specificity for the 2C receptor and in clinical trials did not cause any heart valve problems, and they looked specifically for that,” Greenway noted.

Greenway said Qnexa, which produced the best results in trials, “combines an old drug phentermine in low doses with an anti-epileptic drug, topiramate, which is also used to treat migraines.” He added that topiramate had been looked at as a single drug for weight loss in the past, but it caused confusion. “People would have trouble remembering words, had slow thinking and felt fuzzy-headed.” That has not been the case for those who took Qnexa in clinical trials. “They didn’t seem to have the same issues of mental slowing they had with topiramate alone, and it (Qnexa) seemed to be pretty well tolerated. Sometimes these drug combinations can wind up being a good thing from the side effect perspective.”

Contrave, which is also a combination drug, employs two drugs that both work on addiction issues, according to Greenway. Bupropion is used to treat depression and naltrexone to treat addiction to alcohol or opiates. “Studies with that combination show it acts not only on the hunger centers but also on the reward centers,” he said.

Greenway added that each of these drugs have benefits and provide physicians with the luxury of having options. “All of these drugs are a really good thing for the field,” he said. “I think there is a tendency … especially among the investment community … to want to pick one horse as a winner.” However, he noted, not every patient who is overweight or obese has the same underlying issues. “I think we’re getting to the place where you can start to tailor things.”