Effect of sibutramine on weight maintenance after weight loss: a randomised trial

doi:10.1016/S0140-6736(00)03491-7

The Lancet

Volume 356, Issue 9248, 23–30 December 2000, Pages 2119-2125

https://doi.org/10.1016/S0140-6736(00)03491-7 Get rights and content

Summary

Background

Sibutramine is a tertiary amine that has been shown to induce dose-dependent weight loss and to 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 2 years.

Methods

Eight European centres recruited 605 obese patients (body-mass index 30-45 kg/m²) for a 6-month period of weight loss with sibutramine (10 mg/day) and an individualised 600 kcal/day deficit programme based on measured resting metabolic rates. 467 (77%) patients with more than 5% weight loss were then randomly assigned 10 mg/day sibutramine (n=352) or placebo (n=115) for a further 18 months. Sibutramine was increased up to 20 mg/day if weight regain occurred. The primary outcome measure was the number of patients at year 2 maintaining at least 80% of the weight lost between baseline and month 6. Secondary outcomes included changes in uric acid concentrations and glycaemic and lipid variables. Analysis was by intention to treat.

Findings

148 (42%) individuals in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 sibutramine-treated individuals who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 individuals in the placebo group (odds ratio 4·64, p<0·001). Patients had substantial decreases over the first 6 months with respect to triglycerides, VLDL cholesterol, insulin, C peptide, and uric acid; these changes were sustained in the sibutramine group but not the placebo group. HDL cholesterol concentrations rose substantially in the second year: overall increases were 20·7% (sibutramine) and 11·7% (placebo, p<0·001). 20 (3%) patients were withdrawn because of increases in blood pressure; in the sibutramine group, systolic blood pressure rose from baseline to 2 years by 0·1 mm Hg (SD 12·9), diastolic blood pressure by 2·3 mm Hg (9·4), and pulse rate by 4·1 beats/min (11·9).

Interpretation

This individualised management programme achieved weight loss in 77% of obese patients and sustained weight loss in most patients continuing therapy for 2 years. Changes in concentrations of HDL cholesterol, VLDL cholesterol, and triglyceride, but not LDL cholesterol, exceed those expected either from weight loss alone or when induced by other selective therapies for low concentrations of HDL cholesterol relating to coronary heart disease.

Introduction

The prevalence of obesity has increased substantially over the past 2-3 decades in developed and developing countries.1, 2, 3 The health impact of weight gain is so marked that obesity has now been classified as a major global public-health problem.³ Yet measures to prevent and counteract this medical problem are only now being explored while clinicians continuing to concentrate on handling the physical, cardiovascular, metabolic, reproductive, and psychosocial consequences, rather than tackling the condition itself.

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.⁴ This drug induces dose-dependent weight loss⁵ and, over a year's treatment, can amplify the effects of a very low calorie diet.⁶ We assessed sibutramine's ability to maintain longer-term weight loss by doing a randomised, placebo-controlled, double-blind, parallel-group trial with an open run-in. During the first (open) 6 months, patients underwent a managed weight-reduction phase incorporating sibutramine. Patients in whom appreciable weight loss were achieved went on to the randomised phase, which was designed to assess sibutramine's ability to maintain, over the subsequent 18 months, the weight loss achieved in the open phase.

Section snippets

Patients

Patients were recruited from local health centres and screened medically for their suitability for the trial. They were weighed and measured, and then, on acceptance, assessed for dietary practices and physical activity. They were also fasted overnight (for 14 h) before blood taking and urine examination. Eligible participants were aged 17-65 years with a body-mass index between 30 and 45 kg/m². Obese individuals with recent weight changes or specified diseases-eg, myxoedema; Cushing's

Patients

605 individuals (107 men and 498 women) were recruited (table 1). Almost all patients were white; only were 2% of Afro-Caribbean origin, and 1·5% of Asian descent. Of the total number entering the trial, 499 (82%) completed the first 6-month regimen, 467 (94%) of whom were eligible for randomisation because they had achieved more than 5% weight loss with little or no weight regain on their individualised management scheme (figure 1). During the first phase of weight reduction, 106 patients of

Discussion

The trial shows that almost all patients who persist with the management scheme developed for this trial can achieve at least a 5% weight loss with sibutramine, and over half can lose more than 10% weight within 6 months. Despite most patients having repeatedly tried to lose weight, a feature which usually reduces the impact of any new treatment, the study is unusual in showing an almost linear progressive weight loss throughout the first 6 months. Several factors seem to be responsible: the

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ArticlesEffect of sibutramine on weight maintenance after weight loss: a randomised trial*

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Patients

Patients

Discussion

Clin Endocrinol Metab

Am J Med

Am J Clin Nutr

Lancet

Am J Clin Nutr

Lancet

Am Heart J

The worldwide epidemic of obesity. 8th International Congress on Obesity

Articles
Effect of sibutramine on weight maintenance after weight loss: a randomised trial*