Weight-loss drugs affect appetite and fat absorption

September 1, 2011

A number of different diets are effective in producing some degree of weight loss; the significant issue is how to maintain weight loss over time.

During the past 20 years, there's been a dramatic increase in weight problems in the United States, and currently about one-third of U.S. adults are obese. Doctors agree that the more overweight a person is, the more likely that he or she will have health issues such as heart disease, stroke, high blood pressure, diabetes, osteoarthritis and breathing problems.

Weight problems are assessed using the body mass index (BMI), a calculation based on a person's weight and height. An adult who has a body mass index between 25 and 29.9 is considered overweight, while an adult who has a body mass index of 30 or higher is considered obese.

"Losing even a small amount of weight and increasing physical activity can prevent some of the complications of obesity, particularly type 2 diabetes," says Mark Abramowicz, MD, Editor in Chief of The Medical Letter on Drugs and Therapeutics, a non-profit newsletter that critically appraises drugs. "Diet and exercise are the preferred methods for losing weight, but they are still associated with high long-term failure rates."

MEDICATIONS FOR WEIGHT

Most of the available weight-loss medications approved by the FDA are appetite-suppressant medications. They promote weight loss by decreasing appetite or increasing the feeling of being full, and by increasing one or more brain chemicals that affect mood and appetite.

"Only a few drugs are FDA-approved for treatment of obesity, and all have major drawbacks," says Dr. Abramowicz. "Pharmacotherapy for weight loss should probably be reserved for patients who have a body mass index greater than 30, or who have a BMI greater than 27 plus a comorbidity such as hypertension or diabetes."

The oldest weight-loss drugs are sympathomimetic amines such as methamphetamine, phentermine and diethylpropion. They are all classified as controlled substances, and are only approved for short-term (up to 12 weeks) use. Phentermine was widely used together with fenfluramine until the combination ("phen-fen") was found to be associated with heart valve abnormalities.

"Data on adverse events in weight-loss trials using sympathomimetic amines are limited, but they include increases in heart rate and blood pressure, dry mouth, nervousness, insomnia and constipation," says Dr. Abramowicz.

Orlistat, available both over the counter and by prescription, works by preventing some of the fat in foods from being absorbed in the intestines. Instead, the unabsorbed fat is removed from the body in the stool.

"Used as an adjunct to diet, Orlistat is modestly effective in increasing weight loss," Dr. Abramowicz says. "Patients taking Orlistat 120 mg three times daily for one to four years lost about 5.5 pounds to 7 pounds more than those taking a placebo."

Adverse effects including gas and fecal urgency typically occur after patients eat high-fat foods and are associated with a high incidence of drug discontinuation.

"Clinical trials have confirmed that these drugs can increase weight loss in the first six to twelve months of a calorie-restricted diet, but long-term use of SSRIs can lead to weight gain," Dr. Abramowicz says. "Some patients become heavier than they were at the start of treatment."

Lifestyle changes that combine increased physical activity and weight loss can reduce the risk of type 2 diabetes. One study of more than 3,000 non-diabetic patients found that lifestyle changes carried out over approximately three years were more effective than medications such as Glucophage in preventing diabetes. Another three-year study of lifestyle changes in more than 1,000 overweight patients with an impaired glucose tolerance test found that each kilogram of weight loss (2.2 pounds) produced a 16% reduction in diabetes risk.