Effect Of Sibutramine On Weight Maintenance - Brief Article

Nutrition Research Newsletter,  Feb, 2001  

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Sibutramine is a tertiary amine originally developed as a potential antidepressant, but with weight-loss-inducing properties. These properties are induced by a dual mechanism involving the inhibition of neuronal reuptake of norepinephrine and serotonin at the receptor sites that affect food intake, and the prevention of the decline in energy expenditure during weight loss. This drug induces dose-dependant weight loss and, over a year's treatement, can amplify the effects of a very low-calorie diet. The current study, recently published in The Lancet, was a randomized, placebo-controlled, double,blind, parallel-group trial with an open run-in designed to assess sibutramine's ability to maintain longer-term weight loss.

During the first (open) 6 months, patients (n=605) underwent a managed weight-reduction phase incorporating sibutramine. Patients in whom appreciable weight loss was achieved went on to the randomized phase, which was designed to assess sibutramine's ability to maintain, over the subsequent 18 months, the weight loss achieved in the open phase. Upon entering the study, patients were prescribed a 600-kcal deficit diet based on a macronutrient content of [is less than] 30% fat and 15% protein. An extra 30 min walking per day was advised with advice on behavioral modification. Participants also received 10 mg sibutramine daily. Each patient was seen by a dietitian every 2 weeks and by a physician monthly. The diet was readjusted to maintain the 600-kcal deficit at 3 months by remeasuring the resting metabolic rate and reestimating the physical-activity level.

Participants (n=467) with a 5% or greater weight loss, with less than a 2 kg weight gain from months 4 to 6, were randomly assigned to either a sibutramine group, or a placebo group, on a 3/1 basis, at month 6. Neither the patients nor the doctors could distinguish between the two groups. Dietetic help was given monthly with the option of returning every 2 weeks for additional help. The sibutramine dose (or placebo) was increased to 15mg if more than 1kg weight gain occurred after month 6. If further weight increases occurred, a maximum dose of 20 mg could be introduced.

During the weight maintenance phase, subjects on sibutramine showed a more consistent weight change than the placebo group. Patients in the sibutramine group on average maintained their weight for another year, with slight upward incline in weight thereafter. Of the 204 sibutramine-treated individuals who completed the trial, 43% maintained 80% or more of their original 6-month weight loss compared with 16% of the 57 patients in the placebo group. Of those who entered the weight maintenance phase on sibutramine, 69% maintained at least 5% weight loss 18 months later, 46% maintained 10% weight loss, and 27% maintained their full weight loss. Of the patients that maintained their full weight loss, 40 remained on 15 mg sibutramine, eight were on 15 mg, and a further eight were on the maximum dose of 20 mg. There were substantial decreases in concentrations of serum triglycerides, VLDL cholesterol, insulin, C-peptide, and uric acid, but not in concentrations of LDL cholesterol. These changes were maintained for up to 2 years and were proportional to weight loss. HDL cholesterol concentrations increased substantially after month 6 when body weights in general had stabilized.

The overall long-term benefit of sibutramine now needs to be assessed not only in obese patients, but also in those with lipid disorders where the impact of sibutramine on HDL cholesterol would be particularly interesting. It is prudent to monitor the blood pressure of patients receiving sibutramine so any unusual cardiovascular response can be identified.

W. James, A. Astrup, N. Finer, J. Hilsted, P. Kopelman, S. Rossner, W. Sarls, L. Van Gaal. Effect of sibutramine on weight maintenance after weight loss: a randomized trial. Lancet 356:2119-2124 (Dec 2000) [Correspondence: Prof. W. Philip T. James, c/o International Obesity TaskForce, 231 North Gower St., London, NW1 2NS, UK. E-mail: JeanHJames@aol.com].

COPYRIGHT 2001 Technical Insights, a divison of John Wiley & Sons.
COPYRIGHT 2001 Gale Group