Abstract
Drug therapy for obesity has had a difficult past history. A number of drugs have had addictive or toxic properties that have required discontinuation. Pharmacotherapy for obesity has an important role in those persons who have failed behavioral weight loss attempts or as an adjunct to those attempts. The interest in pharmacotherapy for obesity is an outgrowth of the now general recognition that it is a chronic disease that cannot be cured, but can be treated. Treatment, however, will generally be a life-long affair. The focus on drug therapy is due to the frequent failure of non-pharmacological weight loss programs.
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References
Griffiths RR, Brady JV, Bradford LD (1979) Predicting the abuse liability of drugs with animal drug self-administration procedures: psychomotor stimulants and hallucinogens. Adv Behav Pharmacol 2: 163–208
Bray GA (1993) Use and abuse of appetite-suppressant drugs in the treatment of obesity. Ann Intern Med 119: 707–713
Munro JF, MacCuish AC, Wilson EM, Duncan LJ (1968) Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J 1: 352–354
Guy-Grand B, Apfelbaum M, Crepaldi G, Gries A, Lefebvre P, Turner P (1989) International trial of long-term dexfenfluramine in obesity. Lancet 2: 1142–1145
O’Connor HT, Richman RM, Steinbeck KS, Caterson ID (1995) Dexfenfluramine treatment of obesity: a double blind trial with post-trial follow-up. Int J Obes 19: 181–189
Noble RE (1990) A six months study of the effects of dexfenfluramine on partially successful dieters. Curr Ther Res 47: 612–619
Finer N, Craddock D, Leveille R, Keen H (1988) Effect of 6 months therapy with dexfenfluramine in obese patients: studies in the United Kingdom. Clin Neuropharmacol 11(Suppl 1): S179–S186
Weintraub M, Hasday JD, Mushlin AI, Lockwood DH (1984) A double blind clinical trial in weight control: use of fenfluramine and phentermine alone and in combination. Arch Intern Med 14: 1143–1148
Weintraub M, Sundaresan PR, Madan M, Schuster B, Balder A, Lasagna L, Cox C (1992) Longterm weight control study I (week 0 to 34). Clin Pharmacol Ther 51 (suppl): 586–594
Connolly HM, Crary JL, McGoon MD, Hensrud D, Edwards BS, Edwards WD, Schaff HV (1997) Valvular heart disease associated with fenfluramine-phentermine N Engl J Med 337: 581–588
Connolly HM, McGoon MD (1999) Obesity drugs and the heart. Curr Probl Cardiol 24: 745–792
Brenot F, Herve P, Petitpretz P, Parent F, Duroux P, Simonneau G (1993) Primary pulmonary hypertension and fenfluramine use. Br Heart J 70: 537–541
Roche N, Labrune S, Braun JM, Huchon GJ (1992) Pulmonary hypertension and dexfenfluramine. Lancet 339: 436–437
Atanassoff PG, Weiss BM, Schmid ER, Tornic M (1992) Pulmonary hypertension and dexfenfluramine. Lancet 339: 436
Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, Higenbottam T, Oakley C, Wouters E, Aubier M et al. (1996) Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 335: 609–616
Bray G, Blackburn GL, Ferguson JM, Greenway FL, Jain AK, Mendel CM, Mendels J, Ryan DH, Schwartz SL, Scheinbaum ML et al. (1999) Sibutramine produces doserelated weight loss. Obes Res 7: 189–198
Bray G, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K (1996) A doubleblind randomized placebo-controlled trial of sibutramine Obes Res 4: 263–271
Fanghanel G, Cortinas L, Sanchez-Reyes L, Berber A (2000) A clinical trial of the use of sibutramine for the treatment of patients suffering from essential obesity. Int J Obes 24: 144–150
Davidson MH, Hauptman J, DiGirolamo M, Froeyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J et al. (1999) Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA 281: 235–242
Sjöström L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar H, Krempf M (1998) Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet 352: 167–172
Hauptman J, Lucas C, Boldrin MN, Collins H, Segal HR (2000) Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med 9: 160–167
Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Arnold ME, Steinberg CM (2000) Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo-controlled trial. Obes Res 8: 431–437
Barsh GS, Farooqi IS, O’Rahilly S (2000) Genetics of body-weight regulation. Nature 404: 644–651
Barsh GS, Schwartz MW (2002) Genetic approaches to studying energy balance: perception and integration. Genetics 3: 589–600
Pi-Sunyer FX (1996) A review of long-term studies evaluating the efficacy of weight loss in ameliorating obesity Clin Therapeut 18: 1006–1035
Wadden TA, Sternberg JA, Letizia KA, Stunkard AJ, Foster GD (1989) Treatment of obesity by very low calorie diet, behavior therapy, and their combination: A five-year perspective. Int J Obes 13: 39–46
Wadden TA (1993) Treatment of obesity by moderate and severe caloric restriction: results of clinical research trials. Ann Intern Med 119: 688–693
Pi-Sunyer FX (1983) Medical hazards of obesity. Ann Int Med 119: 655–660
Flegal KM, Graubard BI, Williamson DF, Gail MH (2005) Excess deaths associated with underweight, overweight, and obesity JAMA 293: 1861–1867
Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB (2003) Years of life lost due to obesity. JAMA 289: 187–230
Peeters A, Barendregt JJ, Willekens F, Nusselder W, Bonneux L, NEDCOM, The Netherlands Epidemiology and Demography Compression of Morbidity Research Group (2003) Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med 138: 24–32
Pi-Sunyer FX (1993) Short-term medical benefits and adverse effects of weight loss. Ann Intern Med 119: 722–726
Leibel RL, Rosenbaum M, Hirsch J (1995) Changes in energy expenditure resulting from altered body weight N Engl J Med 332: 621–628
Danforth E, Burger AG (1989) The impact of nutrition on thyroid hormone physiology and action. Annu Rev Nutr 9: 201–227
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425–432
Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S et al. (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1: 1155–1161
Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540–543
Campfield LA, Smith FJ, Guisez Y, Devos R, Burnn P (1995) Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269: 546–549
Myers MG Jr (2004) Leptin receptor signaling and the regulation of mammalian physiology. Rec Progr Harm Res 59: 287–304
Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, Lubina JA, Patane J, Self B, Hunt P et al. (1999) Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282: 1568–1575
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL et al. (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans N Engl J Med 334: 292–295
Ettinger MP, Littlejohn TW, Schwartz SL, Weiss SR, McIlwain HH, Heymsfield SB, Bray GA, Roberts WG, Heyman ER, Stambler N et al. (2003) Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized, dose-ranging study. JAMA 289: 1763–1764
Pi Sunyer FX, Kissileff HR, Thornton J, Smith GP (1982) C terminal octapeptide of cholecystokinin decreases food intake in obese men. Physiol and Behav 29: 627–630
Muurahainen NE, Kissileff HR, Pi Sunyer FX (1993) Intravenous bombesin reduces food intake in man. Am J Physiol 264: R350–R354
Batterham R, Cohen M, Ellis S, Le Roux C, Withers D, Frost G, Ghatei M, Bloom S (2003) Inhibition of food intake in obese subjects by peptide YY3-36. N Engl JMed 349: 941–948
DeFronzo RA, Ratner RE, Han J, Kim D, Fineman M, Baron A (2005) Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 28: 1092–1100
Pacher P, Batkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58: 389–462
Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T et al. (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410: 822–825
Cota D, Marsicano G, Tschop M, Grubler Y, Hachskamm C, Schubert M, Auer D, Yassouridis A, Thone-Reineke C, Ortmann S et al. (2003) The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 26: 2442–2450
Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S, Rio-Europe Study Group (2005) 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 365: 1389–1397
Després JP, Golay A, Sjostrom L (2005) Rimonabant in Obesity-Lipids Study Group. Effects on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 353: 2121–2134
Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J for the Rio-North America Study Group (2006) 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 295: 761–775
Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF, Rio-Diabetes Study Group (2006) Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomized controlled study. Lancet 368: 1660–1672
World Health Organization. Obesity and overweight facts. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/print.html (accessed 18 January 2006)
Yanovski SZ, Yanovski JA (2001) Obesity. N Engl J Med 346: 591–602
Flum DR, Dellinger EP (2004) Impact of gastric bypass operation on survival: a population-based analysis. J Amer Coll Surg 199: 543–551
Santry HP, Gillen DL, Lauderdale DS (2005) Trends in bariatric surgical procedures. JAMA 294: 1909–1917
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Pi-Sunyer, F.X. (2008). Why drugs?. In: Wilding, J.P.H. (eds) Pharmacotherapy of Obesity. Milestones in Drug Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7425-9_1
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DOI: https://doi.org/10.1007/978-3-7643-7425-9_1
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