Pharmacotherapy for obesity
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Obesity is a chronic metabolic disorder that affects one third of American adults. Modest weight losses of just 5% to 10% of body weight, which are achievable with lifestyle modification and pharmacotherapy, can lead to remarkable improvements in many obesity-associated co-morbidities, including dyslipidemia, hypertension, and type 2 diabetes. In this review, the indications for pharmacotherapy and the goals of treatment are discussed, and current and future pharmacologic approaches to the treatment of obesity are examined. Current pharmacologic therapies for obesity are limited, but recent advances in our understanding of the complex and overlapping endocrine pathways that regulate body weight have led to new opportunities for antiobesity drug development. Important drug targets that are highlighted in this review include adipocyte-derived hormones, hypothalamic neuropeptides, and gastrointestinal hormones.
- Ogden CL, Carroll MD, Curtin LR, et al.: Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006, 295:1549–1555. CrossRef
- Vidal J: Updated review on the benefits of weight loss. Int J Obes 2002, 26:S25–S28. CrossRef
- NHLBI Obesity Education Initiative Working Group: The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, MD: National Institutes of Health/National Heart, Lung and Blood Institute/North American Association for the Study of Obesity; October 2000. NIH Publication 00-4084.
- Hansen DL, Toubro S, Stock MJ, et al.: The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction. Int J Obes Relat Metab Disord 1999, 23:1016–1024. CrossRef
- Rolls BJ, Shide DJ, Thorwart ML, Ulbrecht JS: Sibutramine reduces food intake in non-dieting women with obesity. Obes Res 1998, 6:1–11.
- Hansen DL, Toubro S, Stock MJ, et al.: Thermogenic effects of sibutramine in humans. Am J Clin Nutr 1998, 68:1180–1186.
- Arterburn DE, Crane PK, Veenstra DL: The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med 2004, 164:994–1003. CrossRef
- Padwal R, Li SK, Lau DC: Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev 2003, 4:CD004094.
- James WP, Astrup A, Finer N, et al.: Effect of sibutramine on weight maintenance after weight loss: a randomized trial. Lancet 2000, 356:2119–2125. CrossRef
- Vettor R, Serra R, Fabris R, et al.: Effect of sibutramine on weight management and metabolic control in type 2 diabetes: a meta-analysis of clinical studies. Diabetes Care 2005, 28:942–949. CrossRef
- Hutton B, Fergusson D: Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. Am J Clin Nutr 2004, 80:1461–1468.
- Richelsen B, Tonstad S, Rossner S, et al.: Effect of orlistat on weight regain and cardiovascular risk factors following a very-low-energy diet in abdominally obese patients: a 3-year randomized, placebo-controlled study. Diabetes Care 2007, 30:27–32. CrossRef
- Torgerson JS, Hauptman J, Boldrin MN, Sjöström L: Xenical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004, 27:155–161. CrossRef
- Mittendorfer B, Ostlund RE Jr, Patterson BW, Klein S: Orlistat inhibits dietary cholesterol absorption. Obes Res 2001, 9:599–604.
- Rössner S, Sjöström L, Noack R, et al.: Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res 2000, 8:49–61. CrossRef
- Pagotto U, Marsicano G, Cota D, et al.: The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 2006, 27:73–100. CrossRef
- Bluher M, Engeli S, Kloting N, et al.: Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 2006, 55:3053–3060. CrossRef
- Di Marzo V, Goparaju SK, Wang L, et al.: Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001, 410:822–825. CrossRef
- Ravinet Trillou C, Delgorge C, Menet C, et al.: CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 2004, 28:640–648. CrossRef
- Colombo G, Agabio R, Diaz G, et al.: Appetite suppression and weight loss after the cannabinoid antagonist SR141716. Life Sci 1998, 63:113–117. CrossRef
- Osei-Hyiaman D, DePetrillo M, Pacher P, et al.: Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 2005, 115:1298–1305.
- Woods SC: Role of the endocannabinoid system in regulating cardiovascular and metabolic risk factors. Am J Med 2007, 120:S19–S25. CrossRef
- Osei-Hyiaman D, Harvey-White J, Batkai S, Kunos G: The role of the endocannabinoid system in the control of energy homeostasis. Int J Obes 2006, 30:S33–S38. CrossRef
- Liu YL, Connoley IP, Wilson CA, Stock MJ: Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice. Int J Obes 2005, 29:183–187. CrossRef
- Bensaid M, Gary-Bobo M, Esclangon A, et al.: The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol 2003, 63:908–914. CrossRef
- Cani PD, Montoya ML, Neyrinck AM, et al.: Potential modulation of plasma ghrelin and glucagon-like peptide-1 by anorexigenic cannabinoid compounds, SR141716A (rimonabant) and oleoylethanolamide. Br J Nutr 2004, 92:757–761. CrossRef
- Van Gaal LF, Rissanen AM, Scheen AJ, et al.: Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005, 365:1389–1397. CrossRef
- Pi-Sunyer FX, Aronne LJ, Heshmati HM, et al.: Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA 2006, 295:761–765. CrossRef
- Despres JP, Golay A, Sjostrom L, et al.: Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005, 353:2121–2134. CrossRef
- Scheen AJ, Finer N, Hollander P, et al.: Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006, 368:1660–1672. CrossRef
- Curioni C, Andre C: Rimonabant for overweight or obesity. Cochrane Database Syst Rev 2006, 4:CD006162.
- Knowler WC, Barrett-Connor E, Fowler SE, et al.: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002, 346:393–403. CrossRef
- Drucker DJ, Nauck MA: The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006, 368:1696–1705. CrossRef
- DeFronzo RA, Ratner RE, Han J, et al.: Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005, 28:1092–1100. CrossRef
- Kendall DM, Riddle MC, Rosenstock J, et al.: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005, 28:1083–1091. CrossRef
- Riddle MC, Drucker DJ: Emerging therapies mimicking the effects of amylin and glucagon-like peptide 1. Diabetes Care 2006, 29:435–449. CrossRef
- Aronne L, Fujioka K, Aroda V, et al.: Progressive reduction in body weight following treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab 2007, In press.
- Astrup A, Toubro S: Topiramate: a new potential pharmacological treatment for obesity. Obes Res 2004, 12(Suppl):167S–173S.
- Tata AL, Kockler DR: Topiramate for binge-eating disorder associated with obesity. Ann Pharmacother 2006, 40:1993–1997. CrossRef
- Gadde KM, Franciscy DM, Wagner HR, Krishnan KR: Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA 2004, 289:1820–1825. CrossRef
- McElroy SL, Kotwal R, Guerdjikova AI, et al.: Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial. J Clin Psychiatry 2006, 67:1897–1906. CrossRef
- Anderson JW, Greenway FL, Fujioka K, et al.: Bupropion SR enhances weight loss: a 48-week double-blind, placebocontrolled trial. Obes Res 2002, 10:633–641.
- Ahima RS: Adipose tissue as an endocrine organ. Obesity 2006, 14:242S–249S.
- Rosenbaum M, Goldsmith R, Bloomfield D, et al.: Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005, 115:3579–3586. CrossRef
- Otabe S, Yuan X, Fukutani T, et al.: Overexpression of human adiponectin in transgenic mice results in suppression of fat accumulation and prevention of premature death by high-calorie diet. Am J Physiol Endocrinol Metab 2007, In press.
- Shionogi announces positive results from a phase IIa study of S-2367, a novel neuropeptide Y5 receptor antagonist for the treatment of obesity [press release]. Florham Park, NJ: Shionogi USA; July 10, 2006.
- Arena Pharmaceuticals completes enrollment with 3,182 patients in lorcaserin phase 3 BLOOM trial for obesity [press release]. San Diego, CA: Arena Pharmaceuticals; February 5, 2007.
- Hsiung HM, Hertel J, Zhang XY, et al.: A novel and selective beta-melanocyte-stimulating hormone-derived peptide agonist for melanocortin 4 receptor potently decreased food intake and body weight gain in diet-induced obese rats. Endocrinology 2005, 146:5257–5266. CrossRef
- Kowalski TJ, Farley C, Cohen-Williams ME, et al.: Melanin-concentrating hormone-1 receptor antagonism decreases feeding by reducing meal size. Eur J Pharmacol 2004, 497:41–47. CrossRef
- Cummings DE, Overduin J: Gastrointestinal regulation of food intake. J Clin Invest 2007, 117:13–23. CrossRef
- Cummings DE, Shannon MH: Ghrelin and gastric bypass: is there a hormonal contribution to surgical weight loss? J Clin Endocrinol Metab 2003, 88:2999–3002. CrossRef
- Zorrilla EP, Iwasaki S, Moss JA, et al.: Vaccination against weight gain. Proc Natl Acad Sci USA 2006, 103:13226–13231. CrossRef
- Batterham RL, Cohen MA, Ellis SM, et al.: Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003, 349:941–948. CrossRef
- Gantz I, Erondu N, Mallick M, et al.: Efficacy and safety of intranasal peptide YY3-36 for weight reduction in obese adults. J Clin Endocrinol Metab 2007, 92:1754–17577. CrossRef
- Wynne K, Park AJ, Small CJ, et al.: Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int J Obes 2006, 30:1729–1736. CrossRef
- Cohen MA, Ellis SM, Le Roux CW, et al.: Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab 2003, 88:4696–4701. CrossRef
- Pharmacotherapy for obesity
Current Atherosclerosis Reports
Volume 9, Issue 6 , pp 454-462
- Cover Date
- Print ISSN
- Online ISSN
- Current Science Inc.
- Additional Links