Sibutramine is known to be effective in treating obesity. The drug blocks reuptake of noradrenaline and serotonin, promoting satiety. It may also raise a patient's metabolic rate by increasing energy expenditure. Wirth and Krause compared different regimens of sibutramine to determine which was more effective than placebo at promoting weight loss.
Patients 18 to 65 years of age were included in the study if their body mass index was in the obese range (30 to 40 kg per m2). They also were required to have attempted unsuccessfully in the past to lose weight by dietary modification. Patients were excluded if they had heart or metabolic disease, or a history of substance abuse, or if they used any medication influencing weight change.
During the four-week run-in period, patients were given 15 mg of sibutramine daily. If patients lost at least 2 percent of their weight and/or 2 kg during this month, they were considered responders and were randomized to one of three groups. Although each patient received one capsule per day, one group received placebo, one group received sibutramine in a dosage of 15 mg per day, and one group received 15 mg of sibutramine daily for weeks 1 through 12, 19 through 30, and 37 through 48, and placebo during the other weeks. Patients had 10 clinical visits during the study: at baseline, every four weeks for three visits, and then every six weeks through the end of the study. Compliance was evaluated at each visit by counting the remaining pills. Serious adverse events were reported immediately. A global assessment of effectiveness was completed at the end of the study, with choices on the five-point scale ranging from very good to poor to none.
The run-in period involved 1,001 patients. Continuous treatment was given to 405 patients, intermittent treatment to 395 patients, and placebo to 201 patients. Approximately one fifth of all patients did not complete the study; similar proportions of each active treatment group (about 20 percent) dropped out, compared with 27 percent of patients in the placebo group.
During the run-in phase, weight loss was similar in the three groups (average weight loss: 4.2 kg). Patients in the continuous treatment group lost an average of 7.9 kg during the 48-week study period, those in the intermittent treatment group lost an average of 7.8 kg, and those in the placebo group lost an average of 3.8 kg. Patients in the placebo group gained an average of 0.2 kg after the run-in period when they were receiving the active drug.
Women, on average, lost more weight than men in the treatment groups. Weight loss in the continuous treatment group was not significantly greater than that in the intermittent group. Most of the patients and investigators rated the effectiveness of the active treatment as good or very good. The active treatment groups experienced significant decreases in triglyceride levels compared with the placebo group. Adverse events included dry mouth, constipation, headache, and sweating. Fourteen percent of patients had such events during the run-in period. The incidence remained low during the last 44 weeks of the study, with constipation and dry mouth occurring in 4.1 and 1.3 percent, respectively, of patients in the treatment groups.
The authors conclude that sibutramine is a safe and effective agent for promoting weight loss in obese persons. An intermittent treatment regimen is as effective as a continuous regimen but is associated with a slightly better adverse-event profile.