Keeping weight-loss drugs in perspective

by Tyrone M. Reyes, M.D.

Health store shelves are brimming with herbs, supplements, and other products to facilitate weight loss — but the vast majority of them don’t work. Recently, at least in the US, a proven medication that helps modestly with weight loss will join their ranks soon. The application by the pharmaceutical company GlaxoSmithKline to sell a low-dose version of its drug orlistat (Xenical) over the counter has been approved by the US Food and Drug Administration (FDA). It will be marketed as Alli. In the Philippines, Xenical is marketed by Roche (Philippines), Inc. Orlistat would be the first weight loss medication in the US to make the switch from prescription to non-prescription status.

In data presented recently at a US national obesity meeting, researchers reported that 36 percent of overweight people taking a low-dose version of orlistat lost more than five percent of their initial body weight, compared with 28 percent of people taking placebo. The researchers also found that users did not abuse the drug by, for instance, exceeding the maximum dose.

The approval to allow orlistat to be sold over the counter reflects the growing concern over the obesity epidemic and the need to make a variety of weight-loss tools easily accessible to consumers. We certainly need new weight-loss solutions as the problem of obesity grows larger and larger, putting millions of overweight or obese people at risk for several major medical conditions and even premature death. Even modest weight loss can reduce these risks. But as most of us know, losing weight can be extremely difficult and keeping it off, even more so. Most people who shed pounds regain them within five years. Little wonder then that there’s intense interest in drugs to boost weight-loss efforts.

But the reasons for weight problems are complex. Genetic makeup, hormones, brain chemistry, environmental influences, and psychosocial pressures all contribute. No pill can melt away fat or keep off the pounds. And the drugs currently prescribed for weight loss don’t do the job by themselves. But for people whose health is at risk and who are struggling to reduce through diet and exercise, drug therapy may increase the odds of success. Experts agree that weight-loss drugs, which all have side effects, are not for the mildly overweight or those who just want to lose a few pounds to improve their appearance (please refer to Ideal Weight Chart).

Recent History Of Weight-Loss Drugs

Over the past few years, researchers have learned a lot about the biological causes of weight disorders. They’ve identified dozens of genes and begun to discover how these genes influence the many systems that affect weight. Weight-loss drugs can temporarily manipulate these systems. For example, sibutramine (Reductil) and phentermine (Duromine, Ionamin) suppress the appetite while orlistat (Xenical) reduces fat absorption. Some 100 new drugs are currently in the testing phase.

Weight medications have a history of failure and safety concerns. In the 1950s and 1960s, dieters took amphetamines to quell their appetites and boost their metabolism — until it was discovered that the pills were addictive and caused paranoia. The combination of fenfluramine and phentermine — popularly known as fen-phen — was widely used in the mid-1990s, until it and another drug, dexfenfluramine, were linked to heart valve disease and subsequently withdrawn from the market. (Phentermine alone is still used.)

Until sibutramine was approved in 1997 for long-term use in obesity, the FDA had required that most of such medications be prescribed for no longer than three months. Both sibutramine and orlistat are approved for use up to one year, but physicians, at their discretion, may prescribe them for longer. Sibutramine is considered effective and safe for up to two years, although it can increase blood pressure and thus requires monitoring. Orlistat, which inhibits the body’s ability to absorb fats, can interfere with the absorption of fat-soluble vitamins. Moreover, there’s little safety data on the use of weight-loss drugs beyond two years.

On the other hand, these medications have a role to play in medical treatment, especially now that obesity is recognized as a metabolic disease and not a failure of desire or willpower, as once thought. Clinicians are finding that obesity, like other chronic conditions, is often easier to manage with a judicious use of medications.

How do they work?

The prescription weight-loss medications now on the market generally fall into one of three categories:

• Noradrenergic agents. These medications increase levels of norepinephrine (also known as noradrenaline), a brain chemical that helps regulate appetite. Phentermine is the safest. On average, people taking phentermine lose two to 13 pounds over a six-month period. After that, weight loss tends to level off — as it does with other diet drugs — for reasons that aren’t entirely clear. These drugs have several side effects; patients should be re-evaluated after three months before continuing on them.

• Serotonin-norepinephrine reuptake inhibitors. The only weight-loss drug in the category is sibutramine (Reductil). It works by increasing the availability of serotonin and norepinephrine. Both brain chemicals make people feel full. Initial weight loss with sibutramine predicts long-term response to the drug: One study showed that people who lost more than four pounds in the first month were more likely to lose 10 percent of their body weight after one year than those who lost less initially.

• Lipase inhibitor. The only lipase inhibitor in the Philippines is orlistat (Xenical), which works by blocking the action of lipase, an enzyme released by the pancreas to help digest dietary fat. In a two-year trial, those who used orlistat had average weight losses over 20 percent better than participants who received placebo — and more than 50 percent greater success in keeping weight off.

Certain antidepressant drugs are prescribed on a short-term basis because they’ve been found to help some people lose weight. But their effects are unpredictable and, in some cases, they may produce weight gain rather than weight loss.

How should they be taken?

The US National Institutes of Health (NIH) guidelines make clear that weight-loss drugs should be used only in combination with lifestyle modifications. There are several reasons for this. To lose weight requires recognizing and changing the behaviors that led to the weight gain. For example, many people gain weight because they’re in situations such as business travel that can trigger overeating and disrupt the body’s normal cues for hunger and satiety. Balancing the demands of job and family can lead to a reliance on prepared foods, take-outs, and restaurant meals, which are usually high in calories than homemade meals. Others eat in response to stressful or emotionally challenging situations. And many people don’t expend enough calories because they don’t incorporate enough physical activity into their daily lives.

Drug therapy works better when it’s paired with an overall program of lifestyle change. A study published in the November 17, 2005 issue of the New England Journal of Medicine found that after one year, sibutramine-takers who participated in a comprehensive counseling program that promoted a low-calorie diet and 30-minute daily walks lost twice as much weight as subjects who received counseling alone or sibutramine alone. The counseling component of the study involved 10 months of regular meetings led by mental health professionals who utilized the LEARN (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition) program for weight management.

Among its important benefits, counseling can help establish realistic goals. The idea behind using weight-loss medications is to improve health and reduce disease risk, not to achieve an “ideal body weight”. A five to 10 percent reduction in weight over time is one common goal. But even more modest weight loss helps. One study of obese women found that those who intentionally lost any amount of weight experienced a 40 to 50 percent decrease in death from obesity-related cancers and 30 to 40 percent decline in death from type 2 diabetes.

What now?

New understanding of the complexities of weight regulation may eventually lead to more targeted therapies. The key to long-term weight loss is effort on many fronts. The US National Weight Control Registry has found that successful “losers” join support groups, exercise intensively, restrict the amounts and kinds of food they eat, and weigh themselves often.

Source: Philippine Star