Abstract
Medicating for treatment of obesity can be a useful adjunct to diet and exercise and can help selected patients achieve and maintain meaningful weight loss. A report from the Heart, Lung and Blood Institute of the National Institutes of Health entitled Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report (1) emphasizes the need for physicians to address obesity in their patients. This report sanctions the clinical use of weight loss drugs approved by the US Food and Drug Administration (FDA) for long-term use as part of a concomitant lifestyle-modification program. Appropriate patients include those who have been unsuccessful in previous weight-loss attempts and whose BMI exceeds 27 kg/m2 who have associated conditions such as diabetes, hypertension, or dyslipidemia, or whose BMI exceeds 30 kg/m2. Still, for many physicians, treatment of obesity is not a routine part of their clinical practices, in part because of the stigma associated with medication usage.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
National Institutes of Health, National Heart, Lung, and Blood Institute. Clinical Guidelines on the Identification, Evaluation, and treatment of overweight and obesity in adults—the Evidence report. Obes Res 1998; 6:51S–210S.
Bray GA, Greenway FL. Current and potential drugs for treatment of obesity. Endocr Rev 1999; 20:805–875.
Weintraub M, Bray GA. Drug treatment of obesity. Med Clin North Am 1989; 73:237–249.
Cole JO, Levin A, Beake B, Kaiser PE, Scheinbaum ML. Sibutramine: a new weight loss agent without evidence of the abuse potential associated with amphetamines. J Clin Psychopharmacol 1998; 18(3):231–236.
Bray GA. Obesity—a time-bomb to be defused. Lancet 1998; 352:160–161.
Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337:581–588.
Ryan DH, Bray GA, Helmcke F, et al. Serial echocardiographic and clinical evaluation of valvular regurgitation before, during, and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine. Obes Res 1999; 7:313–322.
Jick H. Heart valve disorders and appetite-suppressant drugs. JAMA 2000; 283:1738–1740.
Hensrud DD, Connolly HM, Grogan M, Miller FA, Bailey KR, Jensen MD. Echocardiographic improvement over time after cessation of use of fenfluramine and phentermine. Mayo Clin Proc 1999; 74:1191–1197.
Mast ST, Jollis JG, Ryan T, Anstrom KJ, Crary JL. The progression of fenfluramine-associated valvular heart disease assessed by echocardiography. Ann Intern Med 2001; 134:261–266.
McMahon FG, Fujioka K, Singh, BN, et al. Efficacy and safety of sibutramine in obese white and African-American patients with hypertension. Arch Int Med 2000; 160:2185–2191.
Finer N, James WP, Kopelman PG, Lean ME, Williams G. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord 2000; 24:306–313.
Flechtner-Mors M, Ditschuneit HH, Johnson TD, Suchard MA, Adler G. Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results. Obes Res 2000; 8:399–402.
Munro JF, MacCuish AC, Wilson EM, et al. Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J 1968; 1:352–354.
Greenway FL, Ryan Greenway FL, Ryan DH, et al. Pharmaceutical cost savings of treating obesity with weight loss medications. Obes Res 1999; 7:523–531.
Astrup A, Breum L, Tourbro S, et al. The effect and satiety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial. Int J Obes 1992; 16:260–277.
Sjostrom CD, Lissner L, Wedel H, Sjostrom L. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study. Obes Res 1999; 7:477–484.
Foster GD, Wadden TA, Vogt RA, et al. What is a reasonable weight loss? Patients expectations and evaluations of obesity treatment outcomes. J Consult Clin Psychol 1997; 65:79–85.
Bray GA. Evaluation of drugs for treating obesity. Obes Res 1995; 3:425S–434S.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372:425–432.
Bray GA, Tartaglia LA. Medicinal strategies in the treatment of obesity. Nature. 2000; 404:672–677.
National on the Task Force Prevention and Treatment of Obesity. Long-term pharmacotherapy in the management of obesity. JAMA 1996; 276:1907–1915.
Astrup A, Hansen DL, Lundsgaard C, Toubro S. Sibutramine and energy balance. Int J Obes Relat Metab Disord 1998; 22:S30–S42.
Hansen DL, Toubro S, Stock MJ, Macdonald IA, Astrup A. Thermogenic effects of sibutramine in humans. Am J Clin Nutr 1998; 68:1180–1186.
Sykas SL, Danforth E Jr, Lien EL. Anorectic drugs which stimulate thermogenesis. Life Sci 1983; 33:1269–1275.
Lupien JR, Bray GB. Effect of mazindol, D-amphetamine and diethylpropion on purine nucleotide binding to brown adipose tissue. Pharmacol Biochem Behav 1986; 25:733–738.
Scoville B. Review of amphetamine-like drugs by the Food and Drug Administration: Clinical data and value judgments. In: Obesity in Perspective. Pub. No. 75-708. Department of Health, Education, and Welfare, Washington, DC, 1975, pp. 441–443.
Silverstone JJ, Solomon T. The long-term management of obesity in general practice. Br J Clin Pract 1965; 19:395–398.
McKay RHG. Long-term use of diethylpropion in obesity. Curr Med Res Opin 1973; 1:489–493.
Langlois KJ, Forbes JA, Bell GW, Grant GF Jr. A double-blind clinical evaluation of the safety and efficacy of phentermine hydrochloride (Fastin) in the treatment of exogenous obesity. Curr Ther Res 1974; 16:289–296.
Gershberg H, Kane R, Hulse M, Pensgen E. Effects of diet and an anorectic drug (phentermine resin) in obese diabetics. Curr Ther Res 1977; 22:814–820.
Campbell CJ, Bhalla IP, Steel JM, Duncan LJP. A controlled trial of phentermine in obese diabetic patients. Practitioner 1977; 218:851–855.
Williams RA, Foulsham BM. Weight reduction in osteoarthritis using phentermine. Practitioner 1981; 225:231–232.
Yanovski SZ, Yanovski JA. Obesity. N Engl J Med 2002; 346:591–602
Bray GA, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K. A double-blind randomized placebo-controlled trial of sibutramine. Obes Res 1996; 4:263–270.
Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine produces dose-related weight loss. Obes Res 1999; 7:189–198.
Apfelbaum M, Vague P, Ziegler O, Hanotin C, Thomas F, Leutenegger E. Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine. Am J Med 1999; 106:179–184.
Fanghanel G, Cortinas L, Sanchez-Reyes L, Berber A. A clinical trial of the use of sibutramine for the treatment of patients suffering essential obesity. Int J Obes 2000; 24:144–150.
James WPT, Astrup A, Finer N, et al., for the STORM study group. Effect of sibutramine on weight maintenance after weight loss: a randomized trial. Lancet 2000; 356:2119–2125.
Cuellar GEM, Ruiz AM, Monsalve MCR, Berber A. Six-month treatment of obesity with sibutramine 15 mg: a double-blind, placebo-controlled monocenter clinical trial in a Hispanic population. Obes Res 2000; 8:71–82.
Smith IG, Goulder MA. Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity. J Fam Pract 2001;50:505–512.
Dujovne CA, Zavoral JH, Rowe E, Mendel CM. Effects of sibutramine on body weight and serum lipids: a double-blind, randomized, placebo-controlled study in 322 overweight and obese patients with dyslipidemia. Am Heart J 2001; 142:489–497.
Wirth A, Krause J. Long-term weight loss with sibutramine. JAMA 2001; 286:1331–1339.
Fujioka K, Seaton TB, Rowe E, et al., and the Sibutramine/Diabetes clinical study group. Weight loss with sibutramine improves glycemic control and other metabolic parameters in obese type 2 diabetes mellitus. Diab Obes Metab 2000; 2:1–13.
Gockel A, Karakose H, Ertorer EM, Tanaci N, Tutuncu NB, Guvener N. Effects of sibutramine in obese female subjects with type 2 diabetes and poor blood glucose control. Diabetes Care 2001; 24:1957–1960.
Serrano-Rios M, Melchionda N, Moreno-Carretero E. Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy. Diabet Med 2002; 19:119–124.
McMahon FG, Weinstein SP, Rowe E, Ernst KR, Johnson F, Fujioka K. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002; 16:5–11.
Weintraub M, Rubio A, Golik A, Byrne L, Scheinbaum ML. Sibutramine in weight control: A dose-ranging, efficacy study. Clin Pharmacol Ther 1991;50:330–337.
Finer N, Bloom SR, Frost GS, Banks LM, Griffiths J. Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind placebo-controlled study. Diab Obes Metab 2000; 2:105–112.
Hazenberg BP. Randomized, double-blind, placebo-controlled, multicenter study of sibutramine in obese hypertensive patients. Cardiol 2000; 94:152–158
Sramek, JJ, Seiowitz MT, Weinstein SP, et al. Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by β-adrenergic blocking agents: a placebo-controlled, double-blind, randomized trial. Am J Hyperten 2002; 16:13–19.
Berube-Parent S, Prud’homme D, St-Pierre S, Doucet E, Tremblay A. Obesity treatment with a progressive clinical tri-therapy combining sibutramine and a supervised diet-exercise intervention. Int J Obes Relat Metab Disord 2001; 25:1144–1153.
Wadden RA, Berkowitz RI, Sarwer DB, Prus-Wisniewski R, Steinberg CM. Benefits of lifestyle modification in the pharmacologic treatment of obesity: a randomized trial. Arch Intern Med 2001; 161:218–227.
Van Gaal LF, Wauters M, De Leeuw IH. The beneficial effects of modest weight loss on cardiovascular risk factors. Int J Obes 1997; 21(Suppl 1): S5–S9.
Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000; 343:1826–1832.
Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O’Neil PM. Bupropion SR significantly enhances weight loss: a 24-week double-blind, placebo-controlled trial with placebo group randomized to bupropion SR during 24-week extension. Obes Res 2002; 10:633–641.
Haddock CK, Poston WSC, Dill PL, Foreyt JP, Ericsson M. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disord 2002; 26:262–273.
Reife R, Pledger G, Wu S. Topiramate as add-on therapy: pooled analysis of randomized controlled trials in adults. Epilepsia 2000; 41:S66–S71.
Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 2003; 11:722–733.
DiMarzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001; 410:822–825.
Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA 2003; 289:1820–1825.
Montague CT Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387:903–908.
Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341:879–884.
Heymsfield SB, Greenberg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282:1568–1575.
Huckshorn CJ, Saris, WH, Westerterp-Plantenga MS, et al. Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J Clin Endocrinol Metab 2000; 85:4003–4009.
Lambert PD, Anderson KD, Sleeman MW, et al. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity. Proc Nat Acad Sci 2001; 98:4652–4657.
Ettinger MP, Littlejohn TW, Schwartz SL, et al. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized, dose-ranging study. JAMA 2003; 289:1826–1832.
Ludwig DS, Tritos NA, Mastaitis JW, et al. Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 2001; 107:379–386.
Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998; 101:515–520.
Al-Barazanji KA, Arch JR, Buckingham RE, Tadayyon M. Central exendin-4 infusion reduces body weight without altering plasma leptin in (fa/fa) Zucker rats. Obes Res 2000; 8:317–323.
Hauptman J. Orlistat: selective inhibition of caloric absorption can affect long-term body weight. Endocrine 2000; 13:201–206.
James WP, Avenell A, Broom J, Whitehead J. A one-year trial to assess the value of orlistat in the management of obesity. Int J Obes Relat Metab Disord 1997; 21(Suppl 3):S24–S30.
Van Gaal LF, Broom JI, Enzi G, Toplak H. Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Eur J Clin Pharm 1998; 54:125–132.
Sjostrom L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet 1998; 352:167–172.
Davidson MH, Hauptman J, DiGirolamo M, et al. Long-term weight control and risk factor reduction in obese subjects treated with orlistat, a lipase inhibitor. JAMA 1999; 281:235–242.
Hill JO, Hauptmann J, Anderson JW, et al. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Am J Clin Nutr 1999; 69:1108–1116.
Hauptmann J, Lucas C, Boldrin MN, Collins H, Segal KR for the Orlistat Primary Care Study Group. Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med 2000; 9:160–167.
Rossner S, Sjostrom L, Noack R, Meinders AE, Noseda G, on behalf of the European Orlistat Obesity Study Group. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res 2000; 8:49–61.
Lindgarde F, on behalf of the Orlistat Swedish Multimorbidity study group. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity study. J Intern Med 2000; 248:245–254.
Hollander P, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. Diab Care 1998; 21:1288–1294.
Kelley D, Bray G, Pi-Sunyer FX, et al. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes mellitus: a one-year, randomized, controlled trial. Diab Care 2002; 25:1033–1041.
Miles JM, Leiter L, Hollander P, et al. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diab Care 2002;25:1123–1128.
Zavoral JH. Treatment with orlistat reduces cardiovascular risk in obese patients. JHypertens 1998; 16:2013–2017.
Muls E, Kolanowski J, Scheen A, Van Gaal LF. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicenter study. Int J Obes Relat Metab Disord 2001; 25:1713–1721.
Tonstad S, Pometta D, Erkelens DW, et al. The effects of gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. Eur J Clin Pharmacol 1994; 46:405–410.
Linton MF, Fazio S. Re-emergence of fibrates in the management of dyslipidemia and cardiovascular risk. Curr Atheroscler Rep 2000; 2:29–35.
Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circ 2000; 101:207–213.
Heymsfield SB, Segal KR, Hauptman J, et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med 2000; 160:1321–1326.
Tan MH. Current treatment of insulin resistance in type 2 diabetes mellitus. Int J Clin Pract Suppl 2000; 113:54–62.
Ceriello A. The postprandial state and cardiovascular disease: relevance to diabetes mellitus. Diabetes Metabol Res Rev 2000; 16:125–132.
Sjostrom L et al. Xendos. Presentation. International Congress on Obesity, Sao Paolo, Brazil, 2002.
Reaven G, Segal K, Hauptman J, Boldrin M and Lucas C. Effect of orlistat-assisted weight loss in decreasing coronary heart disease risk in patients with Syndrome X. Am J Cardiol 2001; 87:827–831.
Drent ML, van der Veen EA. First clinical studies with orlistat: A short review. Obes Res 1995; 3:S623–S625.
Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Arnold ME, Steinberg CM. Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo-controlled trial. Obes Res 2000; 8:431–437.
Bray GA. Drug treatment of obesity. Endocr Metab Disor 2001; 2:403–418.
Astrup A, Bulow J, Madsen J, Christensen NJ. Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. Am J Physiol 1985; 248:E507–E515.
Astrup A, Breum L, Toubro S. Pharmacological and clinical studies of ephedrine and other thermogenic agonists. Obes Res 1995; 3:537S–540S.
Astrup A, Breum L, Toubro S, Hein P, Quaade F. Ephedrine and weight loss. Int J Obes Relat Metab Disord 1992; 16:715.
Grover GJ, Mellstrom K, Ye L, et al. Selective thyroid hormone receptor-β activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability. Proc Natl Acad Sci USA 2003. Electronic publication in advance of print publication.
Larsen TM, Toubro S, van Baak MA, et al. No thermogenic effect after 28 days treatment with L-796,568, a novel β-3-adrenoceptor, in obese men. Obes Res 2000; 8(Suppl 1):44S.
Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA 1998; 280:1596–600.
Guerciolini R, Radu-Radulescu L, Boldrin M, Moore R. Fecal fat excretion induced by treatment with orlistat or chitosan: a 3-week randomized crossover design study. Obes Res 2000; 8:43S.
Pittler MH, Abbot NC, Harkness EF, Ernst E. Randomized, double-blind trial of chitosan for body weight reduction. Eur J Clin Nutr 1999; 53:379–381.
Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen G, Solomon JL. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001; 25:316–324.
Boozer CN, Daly PA, Blanchard D, Nasser JA, Solomon JL, Homel P. Herbal ephedra/caffeine for weight loss: A 6-month safety and efficacy trial. Int J Obes Relat Metab Disord 2002; 26:593–604.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Humana Press Inc.,Totowa,NJ
About this chapter
Cite this chapter
Bray, G.A. (2005). Pharmacotherapy of Obesity. In: Goldstein, D.J. (eds) The Management of Eating Disorders and Obesity. Nutrition and Health. Humana Press. https://doi.org/10.1385/1-59259-865-X:241
Download citation
DOI: https://doi.org/10.1385/1-59259-865-X:241
Publisher Name: Humana Press
Print ISBN: 978-1-58829-341-1
Online ISBN: 978-1-59259-865-6
eBook Packages: MedicineMedicine (R0)