Core Evidence - Rimonabant: the evidence for its use in the treatment of obesity and the metabolic syndrome
Abstract
Introduction: Obesity and overweight affect over 1 billion people worldwide and are leading causes of morbidity and mortality. Clinical features of obesity converge with those of the metabolic syndrome and type 2 diabetes, greatly increasing the risk of long-term adverse outcomes.
Aims: To review the evidence on rimonabant, a novel CB1 receptor antagonist, for the treatment of obese and overweight patients.
Related Results
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Evidence review: There is clear evidence that rimonabant 20 mg/day in conjunction with a hypocaloric diet causes a mean weight loss of 4.6 kg in obese and overweight patients after 1 year’s treatment, with approximately 50% of patients achieving a weight loss of [greater than or equal to] 5%. One study demonstrated that weight loss is maintained for up to 2 years. The drug also improves lipid and glycemic cardiovascular risk factors, including high-density lipoprotein cholesterol and insulin resistance, and reduces waist circumference, thus reducing the prevalence of metabolic syndrome. Treatment of obese and overweight diabetic patients with rimonabant decreases glycosylated hemoglobin ([HbA.sub.1c]), including patients previously untreated for diabetes. The effect of rimonabant appears to be partly independent of weight loss.
Rimonabant 20 mg/day is generally well tolerated, with mild to moderate transient adverse effects including nausea, diarrhea, dizziness, and anxiety. Approximately 14% of patients receiving rimonabant 20 mg/day discontinued due to adverse effects, primarily depressed mood, although overall rates of depression did not differ significantly compared with placebo.
Place in therapy: The evidence supports the use of rimonabant 20 mg/day along with dietary modification to reduce cardiovascular risk factors in obese and overweight patients, including those with diabetes. The drug is contraindicated in patients receiving antidepressants. Long-term data on cardiovascular outcomes, morbidity, and mortality are eagerly awaited.
Key words: metabolic syndrome, obesity, rimonabant, type 2 diabetes
Scope, aims, and objectives
The increasing worldwide prevalence of obesity and overweight, and the related constellation of risk factors known as the metabolic syndrome (including dyslipidemia, insulin resistance, hypertension, and vascular endothelial dysfunction) are thought to underlie a growing pandemic of cardiovascular disease, diabetes, and certain types of cancer. It is estimated that 90% of type 2 diabetes cases are directly caused by obesity (James & Rigby 2004), and between 112 000 and 280 000 deaths per annum in the USA are attributable to obesity-related disease (Allison et al. 1999; Flegal et al. 2005). In addition to reducing long-term life expectancy, obesity is associated with substantial morbidity, disability, and impairment of quality of life. Comorbidities directly linked with obesity include respiratory difficulties, sleep apnea, infertility, skin disorders, and psychologic dysfunction arising from poor self-esteem (Khaodhiar et al. 1999; Pender & Pories 2005). Interventions to address obesity include appropriate diet, educational initiatives, and exercise. However, drug therapy may be indicated in patients for whom these measures alone are ineffective.
The multifactorial etiology of obesity has sparked numerous lines of research exploring novel therapeutic targets. One such target is the endocannabinoid system, a neuroendocrine pathway involved in the regulation of reward behavior, appetite, and energy homeostasis. Endocannabinoids have physiologic functions in the central nervous system and peripheral organs such as adipose tissue and gut, involving complex modulation and feedback mechanisms (Di Marzo et al. 2001; Pagotto et al. 2005). Evidence from animal models suggests that overactivity of the endocannabinoid system may be associated with obesity, and that blockade of endocannabinoid CB1 receptors is associated with reductions in food intake and body weight (Kirkham & Williams 2004). Rimonabant (SR-141716A; Acomplia[R], Sanofi-Aventis) is a novel CB1 antagonist. This article reviews the evidence of the effectiveness of rimonabant in the treatment of obese or overweight patients, including those with additional cardiovascular risk factors associated with metabolic syndrome.
Methods
The English language medical literature was reviewed for appropriate articles relating to rimonabant for the treatment of obesity and/or the metabolic syndrome. The search terms used were “rimonabant,” “rimonabant AND obesity,” “rimonabant AND metabolic syndrome,” and “rimonabant AND diabetes.” The following databases were searched during July 2005 and then updated in December 2006 as indicated below:
* PubMed, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
* EMBASE, http://www.datastarweb.com
* BIOSIS, http://www.datastarweb.com
* Database of Abstracts of Reviews of Effects (DARE), National Health Service (NHS) Economic Evaluation Database (NHSEED) Health Technology Assessment (HTA), http://www.york.ac.uk/inst/crd/darehp.htm
