NIDDK

The Food and Drug Administration (FDA) approved sibutramine for the management of obesity on November 24, 1997. Knoll Pharmaceutical Company, the manufacturer of the drug, began marketing it in February 1998 under the brand name Meridia^®. Sibutramine is the first anti-obesity drug approved by the FDA since fenfluramine and dexfenfluramine were withdrawn from the market in September 1997 because of evidence of association with the development of valvular heart disease.

The FDA reports that sibutramine helps reduce food intake and is indicated for weight loss and maintenance when used in conjunction with a reduced-calorie diet. The drug is indicated for patients whose body mass index (BMI) is at least 30 (e.g., someone who stands 5 feet 6 inches tall and weighs 185 pounds or more). Sibutramine is also indicated for patients whose BMI is 27 or higher (e.g., someone who stands 5 feet 6 inches tall and weighs 167 pounds or more) if they have other risk factors, such as diabetes, that could improve with weight loss. Patients taking sibutramine are encouraged to make lifestyle changes, including increasing their physical activity and changing their eating patterns. Once a person stops taking sibutramine, he or she is likely to regain the weight unless these new behavior patterns are continued. Sibutramine works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. The appetite-suppressant drugs dexfenfluramine and fenfluramine, which were withdrawn from the market because of findings of valvular abnormalities in some patients, also inhibit the reuptake of serotonin. However, dexfenfluramine and fenfluramine, unlike sibutramine, also release serotonin from cells.

The most common side effects associated with sibutramine are dry mouth, headache, constipation, and insomnia. Sibutramine can also cause a slight increase in blood pressure, and a higher increase in some patients. The FDA recommends that patients taking sibutramine have their blood pressure evaluated regularly, and that people with uncontrolled high blood pressure not take sibutramine. Sibutramine is also not recommended for patients with a history of stroke, heart disease, or irregular heartbeat. In clinical trials, patients who were on a reduced-calorie diet and took 10 milligrams daily of sibutramine over a 1-year period lost an average of 10 pounds; those taking 15 milligrams daily lost an average of 14 pounds. People on a reduced-calorie diet who were not being treated with sibutramine lost an average of 3 1/2 pounds. The Meridia package insert recommends that patients start with a 10-milligram dose per day. If unresponsive, the dose may be raised to 15 milligrams daily. The dose should be lowered to 5 milligrams daily if increased blood pressure or heart rate is noted.

No cases of primary pulmonary hypertension (PPH) or valvular heart disease have been reported in clinical trials of sibutramine. These conditions are rare but serious side effects that have been associated with fenfluramine and dexfenfluramine. Because of the low incidence of PPH in the underlying population, it is unknown whether or not sibutramine may cause PPH. In his address on February 6, 1998, to the National Task Force on Prevention and Treatment of Obesity, Timothy Seaton, M.D., senior medical director for endocrine and metabolic research at Knoll Pharmaceutical Company, reported the results of a cross-sectional, double-blind, placebo-controlled study. In this study, 210 patients received 15 milligrams of sibutramine or a placebo daily for a mean duration of 7.6 months. Echocardiograms on the patients taking sibutramine did not show more valvular disease than those taking a placebo. (About 2 percent of the patients in each group showed valvular disease.)

Donald D. Hensrud, M.D., an obesity expert with the Mayo Clinic, says that the recent discovery of side effects associated with fenfluramine and dexfenfluramine should make people more wary about jumping on diet pill bandwagons. In looking at the long-term use of sibutramine, people will have to balance the benefits of weight loss against side effects such as elevated blood pressure. The resulting effect on overall illness and mortality, if any, probably won't be known for years, according to Dr. Hensrud.¹

Sibutramine costs about $3.40 per day in the Washington, DC, area for patients taking 10 milligrams per day.




¹Reprinted from Mayo Health O@sis (www.mayohealth.org) 1998, with permission of Mayo Foundation for medical Education and Research, Rochester, Minnesota, USA. Mayo Clinic does not specifically endorse any company or product.