Three-Pronged Attack on Obesity
"We really need a Manhattan Project for medical treatment in the field of obesity--we need prevention, we need behavioral modification, we need more drugs, and we need to look at better indications for bariatric surgery," surgeon Dr John Morton (Stanford University, CA) said. Because of the negative social stigma attached to obesity, there is still a lot of reticence among patients, physicians, and the general public to support obesity treatments other than diet and exercise. That must change if the problem is going to be solved, Morton argued. "We need to mainstream the treatment of obesity. That's really the big thing here. We wouldn't be having this conversation around oncology or cardiology. It would just happen. Those patients would get treated."
Exercise More, Eat Less?
In the staged debate, Dr Patrick O'Neil (Medical University of South Carolina, Charleston) was tasked with defending the importance of behavioral modification in preventing and treating obesity. "We all accept that in order to lose weight and keep it off it's going to require changes in caloric changes, changes in eating and drinking habits, and changes in physical activity, including exercise and general lifestyle activity," he said.
We wouldn't be having this conversation around oncology or cardiology
He conceded that "we all know that for a variety of reasons, many physiological and otherwise, it's a lot harder to do than to say. . . . The environment that we live in really does encourage a lot of the wrong things from a weight-control standpoint." However, O'Neil pointed out that lifestyle modification complements the more expensive and perhaps risky measures such as bariatric surgery or pharmaceuticals.
"This is not an either-or recommendation. The [National Heart Lung and Blood Institute] very explicitly recommends that there be a foundation of diet, physical activity, and behavioral activity, or lifestyle changes, even though the patient may in addition be considered for drugs or surgery," because behavioral therapy enhances the impact of surgery or drugs. O'Neil cited studies of several drugs, including sibutramine (Meridia, Abbott Laboratories), showing that although the drug can produce weight loss in obese patients by itself, patients taking the drug while also undergoing behavioral-modification therapy lose even more weight.
Morton, who debated in favor of surgical and device interventions for obesity, said that even surgical patients must be receptive to lifestyle change first. "You need to say that this is a big deal, to change how you live, how you work, how you eat, and how you sleep. And you've got to have those patients on board. I wouldn't offer surgery to somebody who is not ready."
Thinner Living Through Chemistry?
Dr Caroline Apovian (Boston University, MA) is pessimistic about the ability of behavior therapy alone to treat obesity in the majority of patients. "Right now, when you require diet and exercise interventions for at least six months prior to using drugs or surgery, you know the patient is going fail most of the time," she said. "You're just waiting for failure so you can then give them an intervention that is going to work."
Intensive behavior-modification therapy "improves weight loss, but it's not practical on a long-term basis," she said. Apovian cited a 1988 randomized study that showed that although patients who stayed involved in weight-maintenance therapy after six months of weight-loss therapy did not gain back as much as patients who had only six months of weight-loss therapy, the patients in the maintenance-therapy group also started to gain weight again after about a year [1]. She also pointed out that the Institute of Medicine's guidelines on maintenance of weight loss recommend 90 minutes of exercise a day, which is just not practical for most severely obese patients, she said.
We've created a society where it's easy to gain weight. . . . How are we going to change it? Tear down all of the fast-food restaurants?
"We've created a society where it's easy to gain weight, and we can't change it right now," Apovian said. "How are we going to change it? Tear down all of the fast-food restaurants? It's very easy to eat 3000 calories a day or more, so why are we torturing people? Some people really can't make lifestyle changes in this environment, and if we really think that obesity is a disease, let's treat it like one."
Drugs intended to treat obesity are having a difficult time reaching the US market lately. The FDA recently declined to approve Contrave (Orexigen Therapeutics), a combination of naltrexone and bupropion HCL, despite the favorable vote by the FDA's advisory panel. Lorcaserin (Arena Pharmaceuticals) and phentermine/controlled-release topiramate (proposed name: Qnexa, Vivus) were not favored by the advisory panel.
Despite the recent setbacks, Apovian, who is involved with research on several obesity drugs, argued that pharmaceuticals will play an important role in the treatment of obesity in the near future and could eventually even supplant the surgical options, which "just aren't appealing to most patients," she said. "The majority of obese Americans need something in between diet and exercise and gastric bypass or the Lap-Band [Allergan]," she said.
Current surgery and device-based techniques are designed to alter patient's perceptions of satiety and appetite. Eventually, better understanding of endogenous signaling of appetite-regulating hormones and neurotransmitters will allow drug therapy to accomplish the same goal safely, she predicts.
"But in the interim, as we develop drug combinations and new drugs for obesity, we will have devices that are safer and less aggressive than surgery, like the Lap-Band and the EndoBarrier endoluminal barrier [GI Dynamics], to bridge the gap until we figure out which drug combinations simulate what we see with surgery," she said. "Right now, surgery is the only option we have for severe obesity."
Apovian cautioned that although drugs and surgery can kick-start the weight-loss process, ultimately the patient must change his or her lifestyle. "There are combinations of drugs or surgery to help the patients suddenly be able to make lifestyle changes," she said.
O'Neil, Morton, and Apovian support a staged approach to treating obesity. It is hoped that people headed toward severe obesity can be identified early and treated with lifestyle changes alone, but for the foreseeable future, there will be severely obese people in need of more intensive therapy, they agreed. Morton said that, for example, a very small percentage of people who could benefit from weight-loss surgery are currently undergoing the procedure.
"Too many people who need help don't get it," he said. "What we really need is better access to care and to try to make some of those changes earlier rather than later and find out what works and doesn't work."
O'Neil has research relationships with Arena Pharmaceuticals, Orexigen Therapeutics, Weight Watchers International, South Carolina Research Authority, Novo Nordisk, and Shire Development and is an advisor to Orexigen Therapeutics. Apovian is on the scientific advisory board for GI Dynamics, Gelesis, Zafgen, Orexigen, Arena, and Amylin; receives research support from Amylin; and consults for Vivus. Morton reports grants from Ethicon Endosurgery and advises Vibrynt.
http://www.medscape.com/viewarticle/751220?sssdmh=dm1.724644&src=nldne
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