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Can Drugs Make Americans Lose Weight? Not Likely

Diet drugs have proven to be ineffective and sometimes dangerous. Yet more keep coming down the pipeline.
 
 
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"I have taken this drug off and on for the past 10 years for weight loss. It works, but the results NEVER last, it makes you feel great for about six months, you lose weight, you have awesome energy to work out and then it begins to not work anymore. It's like you build up an immunity to it or something."

The comment is about phentermine (Fastin, Adipex, Ionamin), half of a new drug under consideration by the FDA, but it could apply to all the diet drugs. Thanks to human's "thrifty gene," diet drugs work until they don't work, say scientists. When the body senses it's losing its adipose stores, it actually changes the metabolic rules to retain saddlebags and love handles. Thanks for that.

So, even though two-thirds of American adults are overweight and a third obese, few drugs have been able to make a dent in our gross national product; they've proved to be ineffective and sometimes dangerous.

Fen-phen was withdrawn 13 years ago for killing at least 120 people...and it didn't even work that well, people say.

Meridia, one of the few diet drugs currently on the market, was given heart attack and stroke warning from the FDA earlier this year and only works with diet and exercise anyway, users say. Both sound like the joke about the restaurant that had such bad food...and such small portions.

And let's not even talk about Alli and Xenical which, by blocking the body's absorption of fat, cause "oily bowels" and "anal leakage" yet produced no more weight loss than a placebo. (And the FDA just added a "severe liver injury" warning.) "With allies like this, who needs enemas?" comedians quipped.

So when an FDA advisory committee considered a new diet superdrug called Qnexa this month, many put down their Pirate's Booty and listened. Especially when patient Erin Aycock testified she lost 50 pounds during trials and others were said to lose 10 percent of their body weight.

Qnexa, made by California biotech Vivus, combines Topamax, an anti-seizure drug also given for pain and bipolar disorder, with phentermine (the phen in Fen-phen).

Topamax makes you lose weight all right, say patients on the drug-rating site askapatient.com -- along with your memory, your word recall and your hair. In fact Topamax's brain-zapping properties are so well known it is referred to as "Stupamax" in the military where it is in wide use, according to Army Times.

Topamax's weight loss properties may come from the fact that it makes food and beverages tastes bad, say 33 users. Last year it received an FDA suicide warning (along with other seizure drugs) and a few years ago, a warning for acute myopia associated with a type of glaucoma.

What about the amphetamine-related phentermine, the other drug in Qnexa? "I honestly can't distinguish this drug from Adderall, or even cocaine. It might as well be called Prescription Coke," says one phentermine user. Users report losing 50 to 60 pounds (many gaining it back) while being unable to sleep, and chewing gum -- and the insides of their cheeks -- constantly.

Will American soon get a chance to lose weight on Qnexa, albeit while lying awake and biting their cheeks? Maybe. The FDA advisory committee voted 10 to six against Qnexa because of concerns about depression, memory-loss, birth defects, and lack of long-term data. But the committee only makes recommendations and the final FDA decision comes in October.

Meanwhile, two other diet drugs soon come before the FDA, also made by California biotech firms.

In December, an FDA advisory committee will consider Contrave, another combination of already approved drugs that mixes the well-known antidepressant bupropion (which is also an antismoking drug) and the drug naltrexone, which is used to manage opioid and alcohol addictions.

Contrave addresses "both physiological and behavioral drivers of obesity" says its manufacturer, Orexigen, though a cynic on the business site Minyanville writes "An obesity drug that treats depression and addiction; why not just call it another antidepressant?"

In data presented last month at the American Diabetes Association meeting, patients on Contrave for 56 weeks lost at least 5 percent of their body weight (under 5 percent is not considered better than diet and exercise) and in a 24-week study there was also an improvement in "depressive symptoms accompanied by weight loss and improved control of eating in overweight and obese patients with major depression."

Bupropion (Wellbutrin, Zyban), one of the two drugs in Contrave, lacks the weight gain associated with other antidepressants (hopefully --  if it's supposed to be a diet drug) but carries a risk of seizures. And before you suggest its manufacturer raid the competition's Topamax, Orexigen is way ahead of you and already developed a related diet drug with an antiseizure agent built in.

The third drug, called lorcaserin, is also antidepressant-like -- ironically, it's similar to the mood-improving ingredient in Fen-phen that was withdrawn -- and is also the only drug that is truly new. According to an article in the July 15 issue of the New England Journal of Medicine, almost half of patients on lorcaserin for a year lost 5 percent or more of their body weight and 70 percent maintained the weight loss in the second year (while still taking lorcaserin). The FDA worried that lorcaserin would cause heart problems since it's so similar to the withdrawn fenfluramine ("Fen") but it didn't in trials, says the manufacturer, Arena. Lorcaserin goes before an FDA advisory committee in September.

Clearly, lorcaserin and Contrave are safer than the superdrug Qnexa -- but they also cause half the weight loss! Why must a diet drug risk your health to make you lose weight?

"We've found (over and over) that human feeding behavior is protected by multiple, overlapping redundant pathways," says chemist Derek Lowe on his blog, In The Pipeline. "We are the descendants of a long line of creatures that have made eating and reproducing their absolute priorities in life, and neither of those behaviors are going to be altered lightly. The animals that can be convinced to voluntarily eat so little that they actually lose weight, just through modifying a single biochemical pathway, are all dead. Our ancestors were the other guys."

That's why even though patient Erin Aycock told the FDA advisory committee that Qnexa was like "instant willpower" and she "had the ability for the first time in my life to say 'I don't even care if I eat that cookie,'" she gained the weight right back when she went off the drug.

And others gain the weight back while still on drugs. "Extreme weight loss!! I looked emaciated and everyone thought I was on drugs! My dad thought I had cancer, that's how skinny I became," writes a Topamax user on askapatient. "The weight loss died down though after about two years or so. Maybe more a year and half. Now I am as big as a house."

Until scientists find a way to trump the feeding behavior of our ancestral heritage with its "multiple, overlapping redundant pathways," new diet drugs will probably not be the solution for weight loss. And "bad food, small portions" will continue to be the problem.

Martha Rosenberg frequently writes about the impact of the pharmaceutical, food and gun industries on public health. Her work has appeared in the Boston Globe, San Francisco Chronicle, Chicago Tribune and other outlets.
 
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