Get Ready for More Weight-Loss Drugs. But Will They Work?

Given the size of the obesity problem in the United States—and, increasingly, around the world—you'd expect the weight-loss drug market to be, well, huge. It's not. According to the market research firm Datamonitor, while the global market for drugs to combat diabetes will hit a projected $37 billion by 2018, the obesity drug market is likely to come to just $600 million. The reasons? A history of drugs haunted by sometimes dangerous side effects (including, most recently, the risk of heart problems associated with sibutramine, sold under the Meridia name in the United States, for some people with health issues) and the complex physiology of weight regulation.
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Yet, ever cognizant of the market opportunities that would greet a safe, effective drug, manufacturers are teeing up new attempts. Two companies have filed for Food and Drug Administration approval for their medications, and another is expected to file this year. Other drugs are further back in the pipeline. And researchers are urging the exploration of new avenues that may lead to entirely different pharmaceutical approaches to making weight loss easier (although probably never easy).

Shouldn't the obese lose weight the old-fashioned way, through diet and exercise? In an ideal world, probably, but that approach hasn't been particularly successful over the years (see Do Program Diets Work? Rarely—Here are 7 Tips to Shed Pounds). But if willpower alone isn't the answer, neither is treating obesity as a chronic illness to be managed solely through medical means. Behavior and biology both contribute, says Madelyn Fernstrom, director of the nutrition and weight management program at the University of Pittsburgh Medical Center and author of The Real You Diet. Medications, she says, can help make healthful lifestyle choices a bit easier.

But there's not much ammo in currently available prescription options. Phentermine is an appetite suppressant approved by the FDA only for short-term use (up to 12 weeks). It's a stimulant—it was the "good" half of the infamous fen-phen combination that led to dangerous heart and lung damage—and has a powerful but short-lived effect, says Fernstrom. Another drug that muffles appetite, diethylpropion, is also potent but even shorter-acting. Sibutramine is a long-acting appetite suppressant that was initially studied as an antidepressant, but recent data suggest it may cause cardiovascular problems in people with uncontrolled high blood pressure or who have had previous heart attacks or strokes. (The FDA requested a stronger label warning; the European Medicines Agency recommended the drug not be used at all.) Finally, a drug called orlistat (sold over the counter as Alli and by prescription, in a higher dosage, as Xenical) acts not on appetite but by inhibiting a fat-digesting enzyme and causing some of the fat in meals to pass through the digestive tract without being absorbed. If a person eats too much fat, he or she can experience gas, diarrhea, and other unpleasantries. And those are the survivors among weight-loss products; fen-phen spectacularly crashed and burned, while the much-hyped rimonabant was never approved in the United States and faltered in Europe after reports of depression and suicidal thoughts in users. A host of other drugs were abandoned during early studies and never even submitted for approval.

[See Why You Should Think Twice Before Using Alli or Other Weight-Loss Aids.]

With all the drugs, weight loss tends to top out at about 4 to 6 percent of body weight, on average, and then plateaus. Stop taking the drug, and the weight usually comes back. It's not surprising that it's so tough to make the body give up pounds, says John Fernstrom, a professor of psychiatry and pharmacology at the University of Pittsburgh and director of research for the school's Weight Management
Center. Fernstrom, who is Madelyn's husband, has researched weight-loss drugs. Like other physiological processes such as blood pressure, the balance of energy taken in from food and burned off through activity is fairly tightly regulated, he says. (Even if you gain 20 pounds over as many years, all it means is that your body isn't accounting for about 3,500 calories a year, or about 10 calories a day.) But things are lopsided; the body probably has a preference for fat accumulation, allowing weight to creep up far more easily than it creeps down, he says. Our bodies evolved in feast-or-famine conditions; when humans were hunter-gatherers, there was plenty of food available at some times of the year but not at others. So, he says, the pattern was to overeat during times of plenty, store fat, and then burning the fat when food wasn't readily available. Now, of course, conditions are different.

Keeping the percentage of body fat above some critical minimum level is one of the most important biological aspects of our existence, says Rudolph Leibel, a professor of medicine and pediatrics and codirector of the New York Obesity Research Center and the Diabetes and Endocrinology Research Center at Columbia University. Without enough body fat, survival is impaired. So is fertility: Women need enough energy on board to feed themselves and nourish a growing fetus and then, through breast milk, a child. No wonder the body has so many mechanisms in place to protect against too much change in the downward direction. "If you perturb the system in one way, it will compensate in another," says Leibel. "It's very hard to trick Mother Nature."

Will the new drugs currently being developed for the U.S. market work any better or have fewer side effects? Two of them—Contrave, made by Orexigen Therapeutics, and Qnexa, made by Vivus—are actually combinations of existing drugs prescribed for other purposes but married with an eye to boosting effectiveness, reducing side effects, or both. Contrave, expected to be submitted for FDA consideration this year, has bupropion (the ingredient in the antidepressant Wellbutrin and the antismoking therapy Zyban) combined with naltrexone, already prescribed for drug and alcohol addiction. Bupropion seems to stimulate the brain's so-called POMC cells, with the ultimate effect of "decreasing food intake and boosting energy expenditure," says Dennis Kim, senior vice president of medical affairs at Orexigen. Naltrexone, meantime, blocks beta-endorphin, a chemical that normally ratchets down the activity of POMC. The combination leads to "longer and greater weight loss," he says.

Qnexa, which was submitted to the FDA in late December, has produced the largest weight loss in trials. It combines low doses of topiramate, an antiseizure drug, with phentermine. In higher doses, both have side effects—cognitive dulling and fatigue for topiramate and high blood pressure in phentermine—but Peter Tam, president of Vivus, says the combination of the drugs at lower doses reduces those side effects and leads to greater weight loss. (The phentermine is similar to an amphetamine, acting as a stimulant and prompting the release of a neurotransmitter that is linked to appetite suppression. The mechanism behind topiramate isn't understood.)

Lorcaserin, made by Arena Pharmaceuticals, is a new drug that stimulates the serotonin 2C receptor, found mostly in the hypothalamus. This receptor is involved in appetite and food intake. (Fenfluramine, the "bad" half of fen-phen, stimulated the closely related 2B receptor that is found in the heart, with ill effects.) "It's targeting one specific [receptor] subtype that's in a part of the brain which should only affect food intake suppression," says Dominic Behan, cofounder and chief scientific officer of Arena. The drug also seems to have few side effects. Safety will be key for the FDA, given that an obesity drug is likely to find its way into the medicine cabinets of people who may only want to lose 10 to 15 pounds; for them, the risks of carrying the extra weight aren't large, so the risks of the drug better be extremely low, says Donna Ryan, president of the Obesity Society and associate executive director for clinical research at Pennington Biomedical Research Center in Baton Rouge, La. (Her financial relationships with drug and weight-loss companies ended in 2008.)

It's important to have more options, says Michael Cowley, developer of Contrave and a professorial fellow in the department of physiology at Monash University in Australia. He and others use the analogy of the antidepressant market to describe what more drugs would likely mean: a range of different options that work well in some people and not in others—so you try something, see if it works, and move to something else if it doesn't.

Top Ten Weight Loss Tips

"In November 2009, I weigh around 145 pounds. till from there my struggle starts. My struggle for Life, to look slim, to look beautiful, so fit in my favorite one piece dress. Till then from my hard work I am able to lose 45 pounds that too in three and a half months. Then , I thought that I will share my success tips with you all, as I am happy to have helped from my friends and family members. Feel free to add your own tips to this list, too!" -- Julia, Argentina

1. Dietary control and exercise. It’s true what they say – all you need to do is watch what you eat, and expend more energy than you consume. It’s really that simple. You can quit reading this list now, you now know everything you need to know and didn’t need to fork over $500 for the privilege of me telling you the secret of losing weight. You don’t need to read a 4,000 page book, you don’t have to buy a tape series, you don’t need to stay up late at night to watch infomercials to understand this basic premise. It’s 100% true.
2. Change your lifestyle. If you’re calling this a “diet,” then you’re going to gain all the weight back (and more) within a few months of losing it. Diets do not work. Diets are temporary. When you change your dietary lifestyle, however, you’re changing your habits – and you’re putting yourself on track for long-term / continued success and weight maintenance. Don’t ever tell anybody you’re on a diet – ever. I’m speaking from experience, here – a reformed low-carber. Worked out well for a while, but ultimately failed because my entire lifestyle didn’t change (permanently).
3. Take before and after photos. I know it sucks to see yourself as a chunky monkey (sorry, that’s what I called myself – if only to get myself motivated to meet my weight loss goal). However, there’s no easier way to illustrate your progress. The “after” photos are far more fun to capture and share, admittedly. Find yourself on Flickr! It’s good to see yourself how others see you. Do you like how you look? In many ways, Flickr helped me lose weight.
4. Hire a substitute teacher. Don’t reach for the brands you know and love immediately – or without thinking first. Eggs are “good” for you, but consider using egg substitutes instead (in fact, many restaurants will let you order lower calorie foods). There are countless “lower” alternatives for you to try. If something different doesn’t taste good, by all means – find a better substitute, or eat less of the original. In some cases, the substitute may be worse for you than the regular version of the product. The good news is, healthier choices are silently replacing their “normal” counterparts – and they taste just as nice.
5. Identify your exercise. No exercise was created equal. You might like running, so run. You might like jogging, so jog. You might like stationary bikes, so bike stationarily. Find the one that works best for you – that isn’t too much of a chore for you to do regularly throughout the week. Don’t pick a routine that you don’t like – or you won’t want to do it, and you certainly won’t stick with it for long. I also wouldn’t recommend buying into that whole “no pain, no gain” mantra. I’ve lost weight without hurting myself, and you probably can, too.
6. Set realistic goals. You can lose 50 pounds in a week if you work out 12 hours a day and eat nothing but celery – but not if you’re human. Slow and steady wins the race. Don’t bite off more than you can chew – literally. Make small goals on your way to the bigger goal(s). In the end, you’ll have achieved more (and more frequently, might I add).
7. Become a Gazelle. You’ve probably seen Tony Little on TV, selling his Gazelle glider – a low impact exercise machine. I can tell you: it works. It’s easy on my legs, and really gives me a workout when I apply myself on it. Some people say it’s awkward to use, but I love mine – and would consider recommending no other home exercise equipment at this point. Then again, I’m a wimpy geek who only wants to burn calories. 
8.  Avoid trans fats and high fructose corn syrup. I offer this suggestion for a few reasons. First, they’re not good for you anyway. Second, you’ll eliminate a lot of the “bad foods” outright – no questions asked. You’ll have to become more selective in what you eat by avoiding these two nasty ingredients – which are in more foods than you probably care to know.
9. Take a magic pill. Nonsense! There is no such thing as a magic pill. Don’t fall victim to the hype of the latest fat-burning drug commercial. If you listen or read closely, you’ll see that every single one of these things is effective when combined with proper diet and exercise (which they even state in their advertisements). The side-effects for these drugs are usually worse than your additional weight, anyway.
10. Ignore Ronald McDonald. You don’t have to eliminate fast food completely, but you should avoid it at all costs. Most of it is nasty, bad stuff anyway – if you’d even go as far as to call it food. If you’re looking for convenience, find a more convenient meal source. Besides, most of what they serve would be considered “food product,” not food. There’s a gigantic difference as far as your body is concerned. Your bloodstream does not have taste buds, need I remind you?

Hot Health--Losing Weight Means Eating More

Health is hot and getting to your ideal weight is even hotter.  So how can you lose weight by eating more?  It's simple, eat more often and smaller portion sizes.

That means snacks are a good thing!  When you want to lose weight, starving is not the answer, as a matter of fact, if you do not eat often enough you can permanently slow your metabolism.  That means your body will burn fat slower.  But through portion control and frequent eating, you can boost your metabolism, satisfy your hunger and help your body lose weight.

But if you are eating 5 or 6 meals a day, you need to eat healthy.  Fitness expert, explains how your plate should look.  "You should have an inch around the outside of your plate and your food should be about an inch tall." He also adds, "You should have 1 meat, 1 vegetable and 1 carbohydrate."  Your meat (chicken, meat or fish) should only be as big as your fist.
Depriving your body of food will not work and in the end your body will suffer.  Fat diets and starving yourself will throw your body into what fitness experts call "starvation mode".  That means you body will not digest all of your nutrients and instead will store them as fat.  Your body will protect itself because it no longer knows when you will feed it again.

Also, to help you reach your weight goal add in an exercise routine.  You can exercise for 30 minutes 3 to 5 times a week.  If you add in exercise along with extra meals, you will be able to reach your weight goal in no time.

Depression and Anxiety would Gain Weight I

People who suffer from depression, anxiety or other mental health disorders are more likely to gain weight over time, according to a study published in the British Medical Journal.

Mika Kivimaki and colleagues at University College London followed more than 4363 British civil servants aged between 35 and 55 years and not obese at baseline, for 19 years. One questionnaire was administered and their body mass index measured at baseline and three times during the study.

People with symptoms of depression, anxiety or other mental disorders in the three evaluations were twice as likely to be obese at the last evaluation than those who never reported such symptoms.

More symptoms were reported frequently, the risk of becoming obese was important. This link remained even taking this into account in the analysis of risk factors for obesity such as the use of psychiatric drugs associated with weight gain .

Obesity did not increase significantly the risk of depression, anxiety or other mental disorders, as other studies have shown. "This does not mean there is no association, but it seemed much lower in our study," said Kivimaki.

Weight Loss: the Importance of Food in Sight and Quickly Prepared I

Have the sight and reach of healthy foods prepared quickly and can make a significant difference for anyone who wants lose weight. This leads to overeating is not especially hungry or tasty food, according to Brian Wansink, author of "Mindless Eating (Eating without thinking), but the visibility and easy accessibility of food or convenience.

For example, in one study, he placed candy jars of chocolate in the cubicles of office workers. A few days later, he removed the candy six feet. The mere fact that the chocolates were brought closer, on average, to eat five a day. This represented 124 calories per day or 5.5 kilos per year.

"When food is very visible, every time we see, we must make a decision. Do I want to eat or not? We can say 'no' 27 times. But at the 28 th time or the 29 th, we can begin to say 'maybe'. And at the 30 th, 31 th, say 'why not, I'm hungry,' "says Wansink.

"The facility has a similar effect. If it's easy and there is nothing to stop us, we continue until something tells us to stop."

An example of this idea is illustrated by the following experiment. Wansink divided a group of 150 participants in 3 sub-groups, giving them either a box of chips with every 7 th roots were stained red, a box where every 14 th roots were stained red, a box without colored chips.

Participants who received a box without colored chips ate on average 23 chips, those with a box with the 14th roots colored chips ate 15 and those with a box with the 7th roots colored chips ate 10.

The red chips provided what Wansink calls a "break point", an interruption that causes the person to ask if she wants to eat more.

For this reason, he says, containers of chips or cookies at 100 calories help 70% of people eat less. When they finished container, they pause and wonder if they still want.

His studies show that people eat more when:

• Serving dishes on the table;
• They eat straight from the bag or cardboard;
• They eat a large plate or large container;
• They eat while watching TV, car or with friends (because their minds are occupied, preventing wonder if they continue to eat).

"What really influences what we eat, what are the visibility and ease." So advises there to help control weight, it is helping to keep healthy food within reach.

"We want something that's easy. If fruits and vegetables are in sight and scope, there is much more likely that we took that cake wrapped in the freezer."

Inspired By : Importance of Food in Weight Loss Plans

Weight Loss: where to Start?

Again, you're going to lose weight. You have several times in the past taken drastic measures to lose weight (on a diet, exercises intensive) that you have returned once again a regular habit? Or rather you have failed to take actions that produce results?

What works for sustained weight loss is the adoption of eating and physical activity that can be maintained long term.

Successfully integrate the recommendations of experts for a healthy life is a good starting point:

• 30 minutes of moderate exercise (equivalent to walking at a brisk pace) per day
• 5 fruits and vegetables per day
• Reduce fats and sugars
• Increase the fibers (which contribute to satiety)

Decide concrete actions by which you want to start by examples:

• Walk 3 times 10 minutes per day
• Buy those lower in fat (eg cheese)
• Read the labels of some foods to choose lower fat, less sugar
• Cook yourself some food to control the proportions of fat (and quality) and sugar
• Better informed on the daily calorie needs and calories of each food, etc..

To lose weight, according to the results obtained in the balance following the changes made, please continue with the adoption of new habits, for example:

• Add 15 minutes of daily exercise or a special activity once or twice a week
• Continue to improve your balanced diet by providing healthy snacks and your lunch to work,
• Always be available to the salad already prepared
• Add a healthy regular repertoire,
• Counting calories taken in one day using a food diary, ...

Since these habits to maintain long-term goal is to find physical activity and dietary changes that you like.

The autosupervision tool for weight loss can help choose the next action for weight loss and to monitor the process.