Diabetes Forecast

All About Weight Loss

The present and future of the quest to be thinner

By Erika Gebel, PhD , ,

The desire to get rid of fat is not simply a cosmetic matter. Being overweight or obese increases the risk of developing type 2 diabetes and can make blood glucose control more difficult for people with the disease. Cancer, heart disease, and other maladies are also linked to being heavy. And being anything but thin can have societal drawbacks, too, in a culture that can be cruel to the plus-sized.

Of course, knowing that dropping pounds is a good idea for your health and actually shedding weight are two totally different things. As it stands, two-thirds of Americans weigh more than is considered healthy. If it were easy to get thinner, these numbers would, presumably, look a lot different.

Ideally, diet and exercise are the best tactics for weight loss. Eating well and getting regular exercise have myriad benefits both tied to and independent of losing pounds. Though weight loss from these lifestyle changes can be modest, studies have shown that it doesn't take much to help prevent diabetes or improve blood glucose control; just a 5 percent decrease in weight can often help make the body use insulin better.

But what if 5 percent isn't enough? And what if a person is simply unable to even lose that much through diet and exercise? Researchers are continuing to develop medications and surgeries that can eliminate pounds, but unqualified success continues to elude them. Here's where things stand.


Some people try to lose weight with unapproved approaches.
Liposuction is not approved for weight loss. The cosmetic procedure, which suctions fat cells from "problem" areas, is not meant for people who are trying to lose weight, according to the Food and Drug Administration (FDA), nor does it improve blood glucose control. A recent study found that fat cells removed through liposuction crop up elsewhere in the body less than a year later anyway.
Nonprescription diet aids available at drug and grocery stores that claim to help with weight loss are considered nutritional supplements, and therefore aren't subjected to the same rigorous safety and efficacy research (or FDA approval) as prescription weight-loss medications. You should talk to a doctor before trying any of these products. They may interfere with other medications you are taking or just be outright dangerous.
Prescription medications that aren't approved for weight loss but may shed pounds all the same include some that treat diabetes (metformin, exenatide, liraglutide), depression (bupropion, fluoxetine), and seizures (topiramate, zonisamide). Some doctors may prescribe these medications off-label for weight loss.

Hope in a Bottle

The history of weight-loss medications is littered with duds, some of them downright dangerous. "There have been a lot of medications that have come in and out of the market," says Mariela Glandt, MD, an endocrinologist at the Bronx-Lebanon Hospital Center. "We're up against a big challenge. The body does everything it can to conserve fat. Medications have been minimally successful, and it's very frustrating for people."

Drugs that once seemed promising, like sibutramine (Meridia), were pulled from the market because they proved hazardous, particularly to the heart. The Food and Drug Administration (FDA) has taken these lessons seriously and recently declined to approve three other weight-loss medications, either because they were found to be ineffective or because they raised safety concerns.

The few drugs that remain available don't typically result in large numbers of pounds lost. There are two basic types of weight-loss medication: short-term and long-term. Short-term meds, which are potentially addictive, are those approved to be used for 12 weeks or less. These drugs, such as benzphetamine (Didrex), diethylpropion (Tenuate), and phendimetrazine (Bontril), are all amphetamine derivatives that work by suppressing appetite, and can increase blood pressure and pulse rate. Loss of 5 to 10 percent of body weight is typical.

Only one long-term medication is currently approved for use in the United States: orlistat. This medication comes in two varieties, prescription strength (brand name: Xenical) and a weaker over-the-counter version (Alli). Orlistat works by blocking the absorption of fat in the small intestine. As a result, the side effects can include gas and diarrhea. "It's not so easy to take," says Glandt. "A lot of people can't tolerate it." Studies have shown that orlistat can result in 5 to 10 percent weight loss.

In addition to side effects, weight-loss medications only work when you take them—and keep taking them. "That's one of the biggest problems: You stop and the weight comes right back," Glandt says. "I think doctors are reluctant to prescribe these." That reservation, combined with the modest weight loss the medications usually produce, has got pharmaceutical companies on the lookout for the next big thing.

The Next Meds?

You may already be taking one type of medication that, according to Glandt, could be an exciting development in weight loss: a class of injectable type 2 diabetes meds known as GLP-1 agonists. Glandt calls them "a real turning point," adding: "This has changed the way I do diabetes treatment. I finally have a way to improve A1C and help patients lose weight." GLP-1 agonists, such as liraglutide (Victoza) and exenatide (Byetta), are currently being tested as weight-loss agents. A 2009 study in the Lancet found that obese people without diabetes who took liraglutide every day for three months lost an average of 16 pounds, while those on prescription-strength orlistat lost only 9 pounds.

Another weight-loss medication in the pipeline is Contrave, but it suffered a setback in February when the FDA turned down approval, requesting additional safety testing. Contrave is a combination of bupropion, an antidepressant and smoking-cessation aid, and naltrexone, which helps people with addictions remain drug and alcohol free. The two medications are thought to work together to promote weight loss of around 10 percent.

Qnexa, currently under review by the FDA, is another weight-loss medication that combines two drugs that are already on the market: phentermine and topiramate. Phentermine is a short-term weight-loss agent, while topiramate treats epilepsy and migraines. Weight loss in studies is an average 10 percent.

One antiobesity medication in late-stage development combines the diabetes medication pramlintide (Symlin) with a novel drug called metreleptin, an analog of the human hormone leptin that is produced by fat tissue and curbs appetite. A study published in the journal Obesity in 2009 reported that pramlintide/metreleptin led to an average 13 percent weight loss over 24 weeks. However, the drugmakers Amylin and Takeda announced in March that they were suspending trials to investigate a safety concern.

Many of the more than two dozen drugs in development for weight loss work by tweaking brain chemistry. This approach can have unintended consequences, though, as was shown in the case of the weight-loss medication rimonabant. This medication modifies brain chemistry to make eating less pleasurable. It was never approved in the United States but was available for a time in Europe before being withdrawn in 2008 after a series of suicides. "There was impressive weight-loss data," says Glandt, "but unfortunately if you take away pleasure, it can lead to depression."

Surgical Approaches

While weight loss of just 5 to 7 percent has been shown to help people with type 2 diabetes, very heavy people looking to shed large numbers of pounds may find surgery to be more effective. Even modest weight loss through lifestyle changes "takes effort," says Blandine Laferrère, MD, assistant professor of medicine at the Columbia University College of Physicians and Surgeons. "On the other side, if you do bariatric surgery, you get 30 to 40 percent weight loss."

Two types of weight-loss (bariatric) surgery are most common: adjustable gastric banding and gastric bypass. Banding involves fitting a small belt around the stomach and filling the band with saline solution to squeeze the stomach, creating a smaller pouch so that one feels full after eating much less food. Gastric bypass surgery essentially shrinks the digestive tract so that food bypasses about 90 percent of the stomach and much of the small intestine. This digestive reorganization limits both how much a person can eat and the body's ability to absorb nutrients.

Gastric bypass typically leads to faster and more weight loss than banding, plus there is an added bonus for people with type 2 diabetes: While both types of surgery can trigger substantial improvement in blood glucose control, gastric bypass can lead almost immediately to diabetes remission independent of how many pounds are lost. Any diabetes improvement from banding is related directly to weight loss.

However, surgery is inherently invasive, and most experts agree it isn't appropriate for just anyone. "Right now, bariatric surgery is indicated for people with morbid obesity [a body mass index over 40]," says Laferrère. "Almost 5 percent of the U.S. population has this range of BMI [which correlates with body fat], and about a third of those people have type 2 diabetes. This is already a lot of people."

Over the years, doctors have attempted to make surgery less hard on the body, lessening complications and shortening recovery time. Both banding and bypass are usually done laparoscopically, using small incisions and a snake-like camera (a laparoscope) to perform the operation. While this is a real improvement over previous methods, laparoscopic surgery is still surgery and poses real risks, such as infection, a bad reaction to anesthesia, or the need for a second operation because of problems arising from the first. In rare cases, gastric bypass surgery (but not banding) can lead to recurring episodes of severe hypoglycemia (low blood glucose).

Around the Curve

There are a number of surgery-free weight-loss devices in development, though none are ready for prime time. If one or more of these end up being cheaper and safer than surgery, many people who wouldn't consider today's surgical options or be good candidates for them might be interested.

The trick to eliminating the need for an incision may be to introduce a device through the mouth or other orifice. For example, the EndoBarrier Gastrointestinal Liner, which is available in Europe, is a latex tube that goes in through the mouth and is inserted into the upper part of the small intestine. This device attempts to mimic some features of gastric bypass surgery and capture some of its benefits in people with type 2 diabetes. A small study last year in the Annals of Surgery found that the EndoBarrier reduced body weight by an average of 19 percent over three months, plus it improved blood glucose control in seven out of eight people who received the implant. The most common side effects are nausea, vomiting, and upper abdominal pain.

Researchers are testing several other weight-loss techniques. Some are trying ways to "sew up the stomach from the inside to make it smaller," says Laferrère. Another approach is banding without an incision required. There's also a balloon that can be inflated in the stomach and a pill that expands in the stomach, both aimed at generating that full feeling.

Not all new strategies do away with surgery. Gastric pacemakers are implanted next to the stomach and deliver electrical impulses to curb appetite. One such device, Abiliti, was recently approved for use in Europe. According to its manufacturer, Abiliti can detect food or drink intake and in response elicit low-energy electrical impulses to the stomach.

At the end of the day, the safest and most effective ways to lose weight in most cases are diet and exercise. Meanwhile, medical science will surely keep trying to find the holy grail of safe, easy, lasting weight loss. If that effort is ever successful, the payoff in better health would be almost incalculable.



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