Weight-Loss Drugs Don't Fulfill Promise

Not long ago I railed against the many unproven weight-loss products being advertised prominently in newspapers, magazines, and online.

To be fair, though, the two latest FDA-approved weight-loss drugs — orlistat (Xenical or Alli over the counter) and sibutramine (Meridia) — haven't produced spectacular results, either.

A recent analysis of 264 studies that compared people taking either of these two drugs with those taking a placebo found that the drug-takers lost an average of less than 8 lbs., or about 5 percent of their mean total body weight - 6.5 lbs. in the 16 trials of orlistat, and 8 lbs. in the 10 trials of sibutramine.

The authors pointed out that even these modest positive results may be overblown, since 90 percent of the trials were funded by the manufacturers of the drugs themselves. And, as is common with trials of weight-loss drugs, between 30 percent and 40 percent of the subjects dropped out of the studies, possibly due to disappointment with the small weight losses or to side effects from the drugs.

Even such small reductions in weight are, of course, not to be sneezed at. They can lower blood pressure, help to prevent diabetes in people at risk, and improve blood glucose control in those who already have diabetes.

But it is important to recognize that neither of these drugs is the long-awaited "miracle" weight-loss pill. These medications cannot produce the amount of weight reduction needed by most obese individuals unless accompanied by a calorie-restricted diet and exercise.

While both drugs are safe, they can each cause troublesome side effects. Since orlistat works by blocking the action of an intestinal enzyme that digests fats, this undigested fat is lost in the stools. Common side effects include crampy pain, urgency, increased defecation, flatulence, and oily stools. The manufacturer suggests that people taking orlistat take a change of clothes with them to work. Users may also need to take a daily vitamin pill to replace fat-soluble vitamins lost in the stools.

Sibutramine lessens appetite by raising levels of the neurotransmitters serotonin, norepinephrine, and dopamine in the brain. Its most common side effects are dry mouth, headaches, constipation, and insomnia. People with heart disease or uncontrolled high blood pressure are warned to use this drug only with caution because it slightly increases both blood pressure and pulse rate.

What about using these two drugs in combination? In one study, orlistat produced no further weight loss when added to the regimen of obese women who had already been taking sibutramine for one year.

A third weight-loss drug, rimonabant, was also included in the analysis. Rimonabant produced a somewhat greater average weight loss of 10 lbs. compared with the placebo. But this highly promising drug recently failed to obtain FDA approval because it was associated in these trials with worsening depression and anxiety, especially in people with a history of such disorders.