What About Weight-Loss Medications?

With the realization that fenfluramine and dexfenfluramine ("Redux") cause serious heart abnormalities came the likewise realization that there is indeed no "magic pill" for weight reduction. Although I had many patients with dramatic weight loss with "phen-fen" - some over 100 pounds - I had to a great extent stopped using it already because once one quit taking it, the weight came back as fast as it went off! With no changes in eating and exercise habits, and no way to reset the "set point" of body weight, the only people who were really appropriate candidates for this therapy were those who had such high-risk situations that it would have been appropriate for them to take it for life - those with diabetes, hypertension, severe arthritis of the hips and knees, severe chronic back problems, etc. Medical options today are not as effective as was phen-fen, and so have limited usefulness.

Phentermine

Phentermine, the "phen" part of "phen-fen", was not responsible for the heart valve damage or the pulmonary hypertension seen in some who took the combination. Phentermine has in fact been around a long time. It is in the amphetamine class of medications, and works by increasing metabolism and lowering the appetite. It is a little less addictive than amphetamines, but may also tend to show "tachyphylaxis" - requiring an increased dose for the same response over time. The early studies on this drug showed that the average weight loss using it is about seven or eight pounds over that lost when placebos ("dummy pills") are taken. It is cheap, relatively safe when taken for short periods of time, and may be useful as an adjunct during the first few weeks of a serious diet effort to help you "over the hump".

"Meridia" - sibutramine

I am not very impressed with this drug, which is chemically similar in function to some of the newer antidepressants. It attempts to fill the void left by fenfluramine, and offer an "on-label" alternative to Prozac for the physician. (When a drug is used "off-label", such as Prozac to help obesity, that means that there has been no official designation by the FDA that it is safe and effective for that purpose). I am not impressed with the results from studies with this drug when used by itself, and have seen no studies whatsoever suggesting that it be used in conjunction with other agents. The studies which are published in the package insert (by Knoll Pharmaceuticals) show an average weight loss over 24 weeks of 5.3 kg on the maximum dose - but the placebo group lost 1.8 kg, so the difference is 7.7 pounds. That is not much to lose for an expensive pill, and the weight comes back once you quit! What's the point? About 23% of patients lost 10% of their body weight - but again, if you weigh 300 pounds, thirty pounds would be helpful, but you need to keep taking the drug to maintain the loss of that 30 pounds!

Orlistat - "Xenical"

Orlistat is a "fat blocker" - although that name has been used by many in the past to hype various natural products, this drug actually blocks the enzymes in the gut needed to break down and absorb ingested dietary fat. By blocking absorption, the consumed calories do not enter the body. This drug blocks about 30% of the fat consumed. Average weight loss is 18 pounds in a year - not much considering the cost is $120 or so a month, and not much if you really need to lose weight!

There is another way that this drug works, however, and can actually change eating behaviors. Since the rsult of undigested fat in the gut is bacterial fermentation, bloating, gas, discomfort, and occassional leakage of oily liquid stool (with ocassional loss of bowel control!), the user of this drug very quickly learns to stay away from fatty foods. Much like an alcoholic taking antabuse to help with the willpower... I have a few patients who embrace this effect and always eat foods low in fat, and have been quite successful with the drug.

Another problem is that with a reduction in fat absorption comes a reduction in availability of dietary fat-soluble vitamins, so extra supplements will be required to compensate.

"Herbal Phen-Fen"

This refers to a brand name, and also is used generically to refer to natural products which increase metabolism. Many of these products are sold under the rubric "thermogenic". Most contain the herb ephedra, also called Ma Huang and Mormon Tea. Some of these also have caffeine. The active ingredient is ephedrine, a chemical cousin to epinephrine, or adrenalin. They may work to increase metabolism a little bit, but, as one might expect, common side effects include rapid heart rate, shakiness, and elevated blood pressure. There have been a number of reported deaths due to these products - many of these were due to the intentional overconsumption in an effort to lose more weight or to get a "speed-like" effect (one now-banned product was sold under the name "Herbal Ecstasy", suggesting amphetamine-like effects). These products are probably safe to take in moderation, as long as you monitor your blood pressure and pulse rate. They are, however, of limited effectiveness.

Prozac and Related Drugs

Many are suggesting that the combination "Phen-Pro" may be as effective as "Phen-Fen". While it may be, the later became popular after more than a decade of research showed that it appeared to be safe, at least in the short term. After what we learned about fenfluramine, fewer physicians are going to be jumping on the "Phen-Pro" bandwagon - although in reality, the small risk of pulmonary hypertension with fenfluramine should probably not be sufficient to preculde its use by many patients - we routinely prescribe medications with far worse safety profiles! The purported benefit of this combination is the elevated serotonin levels caused by Prozac, which is the same chemical event triggered by fenfluramine. One concern is that many people gain weight on Prozac. While some did not lose weight on "Redux", very few ever gained, so I doubt that this combination will be as effective even if it is safe. Prozac and related medications have a role in treating obsessive-compulsive behavior, and for those who have compulsive eating disorder - from overeating to anorexia nervosa, these medications may have a role.

Leptin

The Amgen Company has synthesized this human hormone and is conducting clinical trials of its use in the treatment of obesity. Preliminary studies indicate that there is a subset of the population which loses significant weight whe receiving supplemental leptin injections. One theory of overweight, based on this hormone which is produced by fat cells and apparently signals the brain about the activity and amount of fat cells, has that people develop leptin resistance, much like some diabetics are so because of insulin resistance. One might expect that giving extra leptin would only be beneficial for a short while if that is the case - increasing leptin triggering increasing leptin resistance. Further studies are starting, and other companies are working on medications which will directly stimulate leptin receptors. These drugs may actually work by "resetting the set-point", and would thus be more likely to be free of side effects. These devlopments are being closely watched and will be reported by the media as they happen.