The Role of Weight Loss Drugs in Fighting Obesity

Image for obesity drugs Despite countless diets, and sincere efforts at weight loss, Americans are getting heavier each year. ]]>Obesity]]> is one of the leading causes of preventable death in the US, second only to tobacco.

Tired of seeing no results from the traditional diet and exercise regime, many people are looking to alternative methods to help them lose weight. Or, put another way, unable to do the hard work of diet and exercise, many people are looking to a drug to help them lose weight. Short of gastric bypass surgery, prescription weight loss medications may be the next best bet for some. But how effective are these medications? And how can you know if you are a good candidate for them?

Available Weight Loss Medications

There are over a dozen prescription and over-the-counter medications used in obesity treatment. Generally, these medications are only prescribed when diet and exercise changes fail to produce the desired results. This is because patients who take these drugs may experience unpleasant side effects or develop a tolerance or addiction to the drugs. However, for some, obesity is increasingly viewed and treated as a chronic illness. For these patients, medication therapy may be required indefinitely.

At present there are two main classes of weight loss medications: appetite suppressants and malabsorption enhancers. To date, only two have been approved for long-term weight loss by the US Food and Drug Administration (FDA): orlistat (Xenical) and sibutramine (Meridia). Another commonly prescribed drug is phentermine, however it’s only suitable for short-term use of a few weeks.

Orlistat

Orlistat (Xenical) is a malabsorption enhancer and works by reducing the net dietary fat absorption by about 30%. This results in a reduced absorption of approximately 200-300 calories per day.
It may cause unpleasant gastrointestinal side effects.
A low-fat diet minimizes side effects. Patients should be informed that excessive fat ingestion may lead to uncomfortable symptoms of gas, cramping, and oily stools.
It reduces absorption of certain vitamins; taking a daily multivitamin is recommended.
There are no recognized contraindications for orlistat.
The two main orlistat trials, both of which lasted two years, resulted in a weight loss of about 9%-10% during the first year compared with 4%-6% for placebo-treated subjects.

Sibutramine

A medication approved for appetite suppression or satiety enhancement class is sibutramine (Meridia).
Sibutramine works by increasing the activity of certain chemicals in the brain: serotonin and norepinephrine, which results in a feeling of satiety.
It's most effective when used in combination with a reduced calorie diet.
The safety and efficacy of sibutramine have been demonstrated in clinical trials. Weight loss in these trials averaged 5%-10% with maintenance of weight loss for up to 18 months.
Sibutramine may cause cardiovascular side effects, such as a small increase in blood pressure and heart rate.
Drug interactions and contraindications should be considered when prescribing appetite suppressants.

Phentermine

Phentermine works by suppressing appetite.
It's most effective when used in combination with diet and exercise.
Common side effects (eg, dry mouth, ]]>insomnia]]> ) tend to be minor and short-lived.
Potential side effects include cardiovascular risks.
Phentermine was part of the “fen-phen” combination that led to dangerous circulatory complications (the other part, fenfluramine, was removed from the market in 1997 due to safety concerns).

Drug Effectiveness and Safety

Unfortunately, there is no “magic pill” for weight loss, and like all medications, they come with the risk of side effects. Additionally, despite rigorous testing, these agents are still new and their safety and effectiveness has not been established beyond one year.

Moreover, weight loss medications generally result in a weight loss of 5-22 pounds per year, with maximum weight loss occurring six months after starting therapy. Of course, even a modest reduction in weight can translate into a significant reduction in obesity-related health risks, such as ]]>diabetes]]> and cardiovascular disease. Most studies suggest that sibutramine or orlistat, combined with diet and exercise can enhance weight loss. And for many individuals, the benefits of losing any weight at all might outweigh the risk.

What the Research Says

Research has focused on the effectiveness of orlistat and sibutramine. Here is a look at some research on these drugs:

A study in the Cochrane Review compared the effectiveness and safety of approved anti-obesity medications in clinical trials of at least one-year duration. The researchers looked at 11 studies on orlistat and five studies on sibutramine and concluded that both appear to be modestly effective in promoting weight loss, but longer and more comprehensive studies are still needed.
Another study, published in the December 2003 International Journal of Obesity and Related Metabolic Disorders, found that orlistat, when combined with lifestyle changes, effectively reduced weight among Mexican-American women, a population at high risk for obesity. In this study, 56 women were randomized to receive orlistat, behavior modification, a low-fat diet, and moderate physical activity for one year, while 52 women were randomized to a wait list control group. This is a small number of test patients, and the benefit of orlistat could not be isolated from the benefits of a low-fat diet, physical activity, and behavior modification.
Researchers have also found that sibutramine may help with maintaining the weight after the pounds have come off—often the toughest part of successful weight loss. The study, published in the August 2003 American Journal of Clinical Nutrition , followed 261 individuals for 18 months after a six-month weight loss phase. The amount of weight initially lost, physical activity, and taking sibutramine all increased the likelihood of maintaining weight loss.

Candidates for Weight Loss Medications

In general, weight loss medications are most appropriate for people whose weight poses a health risk—not those looking to drop a few pounds for aesthetic reasons. Overweight individuals should talk to their doctor or dietitian to determine whether drug therapy is an option for them.

RESOURCES:

American Dietetic Association
http://www.eatright.org

American Obesity Association
http://www.obesity.org

References:

Bays H, Dujovne C. Pharmacotherapy of obesity: currently marketed and upcoming agents. Am J Cardiovasc Drugs. 2002;2(4):245-253.

Klem ML, Wing RR, McGuire MT, et al. A descriptive study of individuals successful at long-term maintenance of substantial weight loss. AJCN . 1997;66:239-246.

Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA . 2004;291(10):1238-1245.

Orlistat. Medline Plus Drug Information. National Institutes of Health website. Available at: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500006.html . Accessed April 20, 2004.

Padwal R, Li SK, Lau DC. Long-term pharmaotherapy for obesity and overweight (Cochrane Review). In: The Cochrane Library, Issue 4, 2003. Chichester: Wiley. CD004094.

Phentermine. Medline Plus Drug Information. National Institutes of Health website. Available at: http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682187.html . Accessed April 20, 2004.

Prescription medications for treatment of obesity. Weight Control Information Network. NIDDK website. Available at: http://www.niddk.gov/health/nutrit/pubs/presmeds.htm . Accessed April 14, 2004.

Treatment: weight loss strategies. American Obesity Association website. Available at: http://www.obesity.org/treatment/weight.shtml . Accessed April 14, 2004.

Van Baak MA, Van Mil E, Astrup AV, et al. Leisure-time activity is an important determinant of long-term weight maintenance after weight loss in the Sibutramine Trial on Obesity Reduction and Maintenance (STORM trial). Am J Clin Nutr . 2003;78(2):209-214.

Wilding J. Clinical Evaluation of anti-obesity drugs. Current Drug Targets . 2004;5(3):325-332.

Last reviewed August 2006 by ]]>Lawrence Frisch, MD, MPH]]>

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.