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Rimonabant: New therapeutic option for managing cardiometabolic risk

Rimonabant: New therapeutic option for managing cardiometabolic risk. Unmet needs in obesity and the metabolic syndrome. Obesity, metabolic syndrome, and diabetes have reached epidemic proportions

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Rimonabant: New therapeutic option for managing cardiometabolic risk

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  1. Rimonabant:New therapeutic option for managing cardiometabolic risk

  2. Unmet needs in obesity and the metabolic syndrome • Obesity, metabolic syndrome, and diabetes have reached epidemic proportions • Increased prevalence of these conditions is projected to have a major impact on CV disease and associated costs of care • Even modest weight loss (5%–10%) can reduce cardiometabolic risk factors • Current behavioral and dietary approaches to weight loss have limited success • New approaches to weight loss are urgently needed Gelfand EV, Cannon CP. J Am Coll Cardiol. 2006;47:1919-26.NIH Expert Panel. Obes Res. 1998;6(suppl 2):51S-209S.

  3. Endocannabinoid system (ECS): Overview Endocannabinoid ligands • Produced on demand • Act locally • Inactivated rapidly • Bind to transmembrane G-protein receptors,principally inhibiting neurotransmitter release Cannabinoid receptor type 1 (CB1) Cannabinoid receptor type 1 (CB1) Cannabinoid receptor type 2 (CB2) Most widespread CB receptor (brain, spinal cord; peripheral nervous system, organs, tissues) Immune cells Gelfand EV, Cannon CP. J Am Coll Cardiol. 2006;47:1919-26.Pagotto U et al. Ann Med. 2005;37:270-5.

  4. Implications of CB1 receptor activation Central nervous system Peripheral tissue Liver GI tract Adipose tissue Skeletal muscle Hypothalamus Limbic system Appetite Motivation to eat/smoke Lipogenesis Altered glucose metabolism Gelfand EV, Cannon CP. J Am Coll Cardiol. 2006;47:1919-26.Pagotto U et al. Ann Med. 2005;37:270-5.

  5. Overview of rimonabant clinical trial programs for the treatment of multiple cardiometabolic risk factors • Rimonabant In Obesity (RIO) • RIO-Europe • RIO-Lipids • RIO-North America (NA) • RIO-Diabetes • Studies with Rimonabant and Tobacco Use (STRATUS) • STRATUS-United States • STRATUS-Europe • STRATUS-Worldwide • Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant—The Intravascular Ultrasound Study (STRADIVARIUS) Gelfand EV, Cannon CP. J Am Coll Cardiol. 2006;47:1919-26.

  6. Rimonabant In Obesity (RIO) program Després J-P et al. N Engl J Med. 2005.Pi-Sunyer FX et al. JAMA. 2006. Gelfand EV et al. J Am Coll Cardiol. 2006. *Hypertension and/or dyslipidemia †RIO-NA: Rimonabant patients re-randomized at 1 year to placebo or continued rimonabant

  7. RIO clinical trial program: Efficacy overview RIO-Europe, RIO-Lipids, RIO-NA; Placebo-corrected change from baseline at 1 year Van Gaal LF et al. Lancet. 2005. Després J-P et al. N Engl J Med. 2005.Pi-Sunyer FX et al. JAMA. 2006. *P ≤ 0.002 vs placebo †P = 0.02 vs placebo

  8. Significant decrease in metabolic syndrome 60 52.9 50 42.2 40 34.8 * Patients * 30 25.8 (%) * 21.2 19.6 20 10 0 RIO-Europe RIO-Lipids RIO-NA Baseline 1 year Rimonabant 20 mg ↓51% ↓39% ↓54% (n = 599) (n = 346) (n = 1222) Van Gaal LF et al. Lancet. 2005.Després J-P et al. N Engl J Med. 2005.Pi-Sunyer FX et al. JAMA. 2006. ATP III criteria *P < 0.001 vs placebo

  9. RIO clinical trial program: Safety and tolerability overview • Most common drug-related adverse event was mild nausea • Rimonabant 5 mg (5.1%–7.2%); 20 mg (11.2%–12.9%) • Adverse event-related discontinuation rate was similar or slightly higher vs placebo • Rimonabant 5 mg (8.3%–9.4%); 20 mg (12.8%–15.0%); placebo (7.0%–9.2%) • Changes in anxiety and depression scores (HAD scale) were similar across treatment and placebo groups Van Gaal LF et al. Lancet. 2005.Després J-P et al. N Engl J Med. 2005.Pi-Sunyer FX et al. JAMA. 2006. HAD = Hospital Anxiety and Depression

  10. Rimonabant: No significant effect on mood HAD scale: Scores at 1 year Van Gaal LF et al. Lancet. 2005. Després J-P et al. N Engl J Med. 2005.Pi-Sunyer FX et al. JAMA. 2006.

  11. Rimonabant: RIO program summary • Over 1 year, rimonabant 20 mg combined with diet demonstrated: • Significant decreases in weight and waist circumference • Weight loss: 14.0–15.3 lbs absolute change, 10.4–12.0 lbs placebo-corrected change • Favorable changes in cardiometabolic risk factor profile Van Gaal LF et al. Lancet. 2005;365:1389-97. Després J-P et al. N Engl J Med. 2005;353:2121-34.Pi-Sunyer FX et al. JAMA. 2006;295:761-75.

  12. Rimonabant: Therapeutic potential • Cannabinoid receptor blockade is a novel approach to treatment of cardiometabolic risk factors • Any degree of weight loss can impact metabolic syndrome and diabetes, ultimately reducing CV risk • Moderate weight loss encourages continued health-promoting behaviors and adherence to medical therapy Gelfand EV, Cannon CP. J Am Coll Cardiol. 2006;47:1919-26.

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