Anorectic Pharmacology Part II: The Absurdity of the New Diet Drugs

by Karlis Ullis, MD with Josh Shackman, MA

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• Part I: Introduction
• Part II: The Absurdity of the New Diet Drugs
• Part III: Are Diet Drugs Necessary?

Both Xenical and Meridia are indicated for obese individuals (BMI greater than 30). So would an already lean bodybuilder trying to reduce his bodyfat even further have any use for either of these drugs? I have not heard of any burgeoning black market in Venice Beach or West Hollywood for either of these drugs, nor have any of my bodybuilding patients asked me for a prescription. Xenical is a big no-no for any bodybuilder, as most bodybuilders already eat relatively healthy and balanced diets. All Xenical will do for them is increase their time in the bathroom and make them lose weight in their wallets.

Meridia may have some hope for bodybuilders, although not much. A couple of studies have shown Meridia to have some thermogenic activity (2). Thus it is possible that Meridia has some muscle sparing activity similar to other thermogenics such as ephedrine. However, the studies on Meridia measure only total weight loss, with no distinction between fat loss and muscle loss. It is possible that Meridia could be used as a mild thermogenic by those who are overly sensitive to ephedrine, but at $100 per month Meridia is probably not worth it for most. This brings me to my next issue:

This is probably the most absurd aspect of these new diet drugs. In general, insurance companies will not "foot" the bill for anti-obesity drugs. Unless you are morbidly obese, you have to pay for these drugs out of your own pocket. The cost for a months supply of either Xenical or Meridia is roughly $100 per month or more.

Let's look at the economics of this. For Xenical, this is a ridiculous price. No trials have yet shown it to be effective in people whose diets are not closely monitored. My guess is that very few people will lose any weight at all from Xenical. So it is basically $100 down the toilet, quite literally considering some of the side effects of this drug.

Next, let's look at Meridia. Let's assume for a second that this drug is as effective as the studies say. Judging by two published studies mentioned above, taking 10-15 mg per day of Meridia for one year will produce anywhere from 6.6 to 9.46 lbs. greater weight loss than you would if you were given a placebo (3). Do the math yourself - at best you are paying $126.85 per pound of weight loss! To make matters worse, you don't know how much of this weight loss is actually from fat and not muscle. And this is all assuming of course that the these studies are actually representative of how well Meridia really works.

Another way to evaluate the cost effectiveness of Meridia is to compare it to other diet drugs. A 1973 review study funded by the FDA did a meta-analysis of 105 studies on various diet drugs. The conclusion of this review study was that these diet drugs available in 1973 (mostly amphetamine-like stimulants) induced patients taking the drugs to lose a half a pound a week more than the placebo group (5). Most of the studies reviewed were short term, none lasting more than a few months. Since this review study was completed, a half a pound a week more than the placebo group has become the standard to evaluate the scientific effectiveness of a diet drug in short term trials.

Short term trials may be the better way to evaluate a diet drug, as After 3-6 months of use a drug may lose its effectiveness. Just about all weight loss drugs and other methods lose their effectiveness after 6 months of use from a combination of lowered resting energy rates and from a decreased energy expended with exercise.

So does Meridia live up to this standard of .5 lbs. per week? Let's look at some of the shorter trials of Meridia to see how it compares to the classic stimulant drugs looked at in the 1973 review study. One of the largest short-term trials on Meridia on 1,047 total patients showed that this is not the case. At 10 mg per day, patients lost .32 pounds a week more than the placebo over 24 weeks. At 15 mg per day, this number moved up to .42 pounds a week more than the placebo - not quite up to par. Only at 30 mg per day did Meridia prove as effective as the "gold standard" of .5 pounds per week more than a placebo (2).

To be fair, some studies did show Meridia to induce a loss of more than .5 pounds a week more than the placebo, but these trials were very short term (12 weeks or less) and had lower sample sizes (1). However, the "kicker" in evaluating Meridia's cost effectiveness is comparing it to far cheaper over the counter diet drugs.

Let's look at phenylpropanolamine (PPA), commonly sold as Dexatrim or Accutrim. Short term trials have shown PPA to be about exactly as effective as Meridia - inducing anywhere from .3 to .5 pounds a week greater weight loss than a placebo (6). PPA cost just "pennies a day", and has an excellent safety profile as well. PPA is not a miracle worker, but will do the trick just as well as Meridia for a tiny fraction of the price.

Another drug to look at is ephedrine. This is a similar drug to PPA (also called norephedrine) which has never been approved as a diet drug. It is sold strictly as a decongestant, but this has not stopped bodybuilders from using it as an energizer and fat burner. When combined with caffeine, ephedrine is at least as effective as Meridia and plenty of trials have showed it to induce .5 pounds more weight loss per week than a placebo (7). Like PPA, it is also just pennies a day to use. More trials need to be done to compare its safety and efficacy compared to PPA.

The pharmaceutical industry has basically failed at finding effective new drugs for treating obesity so far. With the prevalence of cheap and effective drugs such as PPA and ephedrine available, there is really no point in paying $100 per month on drugs that are potentially even less effective. I believe obesity research should refocus itself dramatically to get serious about finding effective treatments.

The Amgen studies so far on Leptin are not that exciting from a fat loss point of view. But they are helping to open the scientific window on the Leptin Resistance Syndrome that the obese seem to have. The story is similar to the insulin resistance picture seen in some types of obesity. But leptin clearly won’t live up to the media’s hype as the new cure for obesity.

One absurd aspect of the research on diet drugs is that 99% of the studies only measure weight loss instead of fat loss. The key to long-term weight loss is keeping the muscle, so only measuring total weight loss is quite useless. New studies should measure both fat loss and muscle loss using new advances in body composition measurement. I believe ephedrine and/or PPA--the Beta adrenergic drug category will prove superior to most diet drugs in this aspect, as thermogenic drugs have been shown to have a strong muscle-sparing effect during dieting. The diet drug industry needs to radically refocus itself from weight loss to fat loss, a concept easily understood by bodybuilders but still somewhat mysterious to diet drug researchers.

Another aspect of diet drug research should be on how to "cycle" diet drugs for optimum effect. The concept of "cycling" drugs is old hat for bodybuilders. The idea is that the human body will adapt to most drugs if taken for too long, so you will get more effect from drugs if you take them intermittently rather than continuously. One study on Phentermine lasting nine months showed that a group taking this drug intermittently in a one-month on, one month off pattern actually lost slightly more weight than a group taking phentermine continuously (7). Since few diet drugs have been shown to induce weight loss for longer than six months, perhaps intermittent "cycles" could prolong the effects of these drugs. Future research should emphasize this concept.

These are just a few ideas for finding an effective treatment for obesity. In Part III of this series, I will go into more detail about what the research says about diet drugs and outline my personal suggestions for fat loss drugs and supplements.