Introduction: Sibutramine is a tertiary amine that has been shown to induce dose-dependent weight loss and enhance the effects of a low-calorie diet for up to a year. We did a randomised, double-blind trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 18 months.
Methods: Eight European centres recruited 605 obese patients (BMI 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) in combination with an individualised dietary deficit programme of 600 kcal/day based on the measured resting rates of energy expenditure. Of these 605, 467 (77%) patients with more than a 5% weight loss were then randomly assigned to 10 mg/day sibutramine (n = 352) or placebo (n = 115) for a further 18 months. Sibutramine was increased up to 20 mg/day if a weight regain occurred.
Results: One hundred and forty-eight (42%) subjects in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 subjects receiving sibutramine who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 subjects in the placebo group (odds ratio 4.64, p < 0.001). Substantial decreases were seen over the first six months in triglycerides, VDL cholesterol, insulin, C peptide, and uric acid; changes, which were sustained in the sibutramine group, but not in the placebo group. Concentrations of HDL cholesterol rose substantially in the second year: overall increases were 20.7% (sibutramine) and 11.7% (placebo, p < 0.001). Twenty (3%) patients were withdrawn because of raised blood pressure; in the sibutramine group, from baseline to two years systolic blood pressure rose by 0.1 mmHg (SD 12.9), diastolic blood pressure by 2.3 mmHg (9.4), and pulse rate by 4.1 beats/min (11.9).
Conclusion: This individualised management programme achieved a weight loss in 77% of obese patients and a sustained weight loss in most patients continuing therapy for two years. Changes in the concentrations of HDL cholesterol, VDL cholesterol, and triglyceride, but not in the LDL cholesterol, exceed those expected either from a weight loss alone or when induced by other selective therapies for low concentrations of HDL cholesterol relating to coronary heart disease.