Effects Of Sibutramine Plus Orlistat In Obese Women

Nutrition Research Newsletter, Oct, 2000

Two medications, sibutramine (Meridia; Knoll Pharmaceutical Co., Mt. Olive, NJ) and orlistat (Xenical; Roche Laboratories, Nutley, NJ), are currently approved by the Food and Drag Administration for weight loss and maintenance of weight loss. Sibutramine is a combined norepinephrine-serotonin reuptake inhibitor, whereas orlistat is a gastric and pancreatic lipase inhibitor. In controlled trials, sibutramine was associated at one year with a 7% reduction in initial weight, and orlistat with a 10% reduction. A study recently explored the benefits of adding orlistat to sibutramine in obese women who had lost an average of 11.6 [ or -] 9.2% of their initial weight during one year of treatment by sibutramine alone.

All of the women (n = 34) continued to receive sibutramine for 16 weeks; in addition, half were randomly assigned to orlistat and the other half to placebo. At baseline (week 52), all patients met with a physician who examined their health and told them to continue to take sibutramine (10 to 15 mg once a day) in the morning. In addition, they were instructed to take one capsule of the investigational medication within [ or -] 1 hour of lunch, dinner, and an evening snack. The researchers decided not to prescribe orlistat in the morning because many of the participants stated that they did not eat breakfast, and the evening snack appeared to present a greater risk for overeating than did breakfast. Patients were instructed to limit their fat intake to a maximum of 20 g per meal (or snack), and 60 g per day, to minimize possible gastrointestinal events, including oily stools, oily spotting, fecal urgency, and related side effects. Patients were also instructed to take a multivitamin every day to prevent possible decreases in levels of fat-soluble vitamins.

All patients met with a registered dietitian or doctoral-level psychologist for five 30-minute sessions during the study period. Patients were prescribed an individualized diet, creating a deficit of approximately 600-850 kcal per day.

Body weight was essentially unchanged in both conditions during the 16-week continuation trial. The addition of orlistat to sibutramine did not significantly increase weight loss (or improve the maintenance of weight loss) as compared with the continued use of sibutramine alone. Patients who had reduced [is less than] 10% during the earlier trial lost 1.2 [ or -] 3.2 kg during the 16-week study, independent of which medication they received. Those who had lost [is greater than] 10% of weight in the prior trial actually gained 1.7 [ or -] 2.6 kg during the 16-week study, resulting in a significant difference between the two groups. Even in highly selected patients, who were thought to be the most likely to benefit from combination therapy, adding orlistat to sibutramine did not increase weight loss. Fifty percent of patients treated by combined therapy reported experiencing soft stool and increased frequency of bowel movements at least one day of the week, as compared with only 9.1% of patients treated by sibutramine alone.

The findings of this study suggest that there may be limits to the amount of weight that most obese individuals can lose (and maintain) with currently approved medications, as well as with behavioral interventions. This limit appears to be 10% to 15% of initial weight. Additional studies are needed to reach definitive conclusions about the possible benefits of combining orlistat and sibutramine.

T. Wadden, R. Berkowitz, L. Womble, et al., Effects of Sibutramine Plus Orlistat in Obese Women Following 1 Year of Treatment by Sibutramine Alone: A Placebo-Controlled Trial, Obes Res 8(6): 431-437 (September 2000) [Correspondence: Thomas Wadden, University of Pennsylvania School of Medicine, 3600 Market St., Ste. 738, Philadelphia, PA 19104. E-mail: wadden@mail.med.upenn.edu.]