Advanced search
Publication Cover
Expert Opinion on Investigational Drugs Volume 11, 2002 - Issue 9
Submit an article Journal homepage
137
Views
36
CrossRef citations to date
0
Altmetric
Review

Anti-obesity drug development

Harold Bays Medical Director/President, Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Ave., Louisville KY, 40213, USA
&
Carlos Dujovne Kansas Foundation for Clinical Pharmacology, Medical Director Radiant Research, Kansas City 12200 W 106th, Suite 330, Overland , Park KS 66215, USA. [email protected]
Pages 1189-1204 | Published online: 24 Feb 2005

Bibliography

  • MOKDAD AH, SERDULA MK, DIETZWH et al.: The spread of the obesity epidemic in the United States. "AMA (1999) 282:1519–1522.
  • MUST A, SPADANO J, COAKLEY EH etal.: The Disease Burden Associated with Overweight and Obesity. "AMA (1999) 282:1523–1529.
  • WORLD HEALTH ORGANIZATION: Obesity: preventing and managing the global epidemic. Report of a WHO Consultation on Obesity, Geneva, 3–5 June, 1997. Geneva: World Health Organization.
  • PATEL MR, MCGUIRE DK: Pounds of prevention: obesity therapy. Am. Heart J. (2001) 142:388–390.
  • KLEIN S: Medical management of obesity. Surg. Clin. North Am. (2001) 81 (5) :1025-1038, v.
  • BERKE EM, MORDEN NE: Medical management of obesity. Am. Fam. Merl (2000) 62(2):419–426.
  • MOKDAD AH, BOWMAN BA, FORD ES et al.: The continuing epidemics of obesity and diabetes in the United States. "AMA (2001) 286:1195–1200.
  • ALLISON DB, FONTAINE KR, MANSON JE et al.: Annual deaths attributable to obesity in the United States. "AMA (1999) 282:1530–1538.
  • KRAL JG: Morbidity of severe obesity. Surg. Clin. North Am. (2001) 81(5):1039–1061.
  • GUMBINER B: The treatment of obesity in Type 2 diabetes mellitus. Primary Care Offic. Practice (1999) 26(4):869–883.
  • POSTON WC, FOREYT JP: Successful management of the obese patient. Am. Fam. Physician (2000) 61(12):3615–3622.
  • DICKERSON LM, CAREK PJ: Drug therapy for obesity. Am. Fam. Physician (2000) 61(7):2131–2138.
  • HENSRUD DD: Pharmacotherapy for obesity. Med. Clin. North Am. (2000) 84(2):463–476.
  • YANOVSKI SZ, YANOVSKI JA: Obesity. NEJM346(8):591–602.
  • •This is an often cited review of obesity treatment.
  • CONNOLEY IP, LIU YL, FROST I et al.:Thermogenic effects of sibutramine and its metabolites. Br. J. Pharmacol (1999) 126(6):1487–1495.
  • WIRTH A, KRAUSE J: Long-term weight loss with sibutramine. JAMA (2001) 286:1331–1339.
  • JAMES WP, ASTRUP A, FINER Net al.: Effect of sibutramine on weight maintenance after weight loss: a randomized trial. Lancet (2000) 356:2119–2125.
  • ••This study, otherwise known as theSibutramine Trial of Obesity Reduction and Maintenance Study (STORM), is one of the major sibutramine studies demonstrating maintenance of weight loss with an anti-obesity drug.
  • DUJOVNE CA, ZAVORAL JH, ROWE E, MENDEL CM: Effects of sibutramine on body weight and serum lipids. Am. Heart J. (2001) 142(3):489–497.
  • LEAN MEJ: Sibutramine: a review of clinical efficacy. Lit. J. Obes. Relat. Metab. Disord. (1997) 21\(Suppl. 1):530–6) 37–39.
  • FUJIOKA K, SEATON TB, ROWE E et al.: Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with Type 2 diabetes mellitus. Diabet. Obes. Metab. (200) 2(3):175–187.
  • FINER N, BLOOM SR, FROST GS et al.: Sibutramine is effective for weight loss and diabetic control in obesity withType 2 diabetes: a randomized, double-blind, placebo controlled study. Diabet. Obes. Metab. (2000) 2(2):105–112.
  • DAVIDSON M, HAUPTMAN J, DIGIROLOAMO M et al.: Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA (1999) 281:235–242.
  • SJOSTROM L, RISSANEN A, ANDERSEN T et al.: Randomized placebo-controlled trial of orlistate for weight loss and prevention of weight regain in obest patients. Lancet (1998) 352:167–172.
  • MITTENDORFER B, OSTLUND R. PATTERSON BW et al.: Orlistat inhibits daily cholesterol absorption. Obes. Res. (2000) 8\(Suppl. 1):43S; 9(10):599–604.
  • 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(9):1321–1326.
  • LINDGARDE F: The effect of orlistat on body weight and coronary heart disease risk profile in obest patients: The Swedish Multimorbidity Study. J. Intern. Med. (2000) 248(3):245–254.
  • ROSSNER S, SJOSTROM L, NOACK R et al.: Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Obes. Res. (2000) 8(1):49–61.
  • STONE NJ, KUSHNER R: Effects of dietary modification and treatment of obesity. Med. Clin. North Am. (2000) 84(1):95–122.
  • WADDEN TA, FOSTER GD: Behavioral treatment of obesity. Med. Clin. North Am. (2000) 84(2):441–461.
  • GULER HP, ETTINGER MP, LITTLEJOHN TW et al.: AXOKINE° causes significant weight loss in severely and morbidly obese subjects. Int. J. Obes. Relat. Metab. Disord. (2001) 25:S111, P291.
  • WEINSTEIN SP, VICARY C, ETTINGER MP et al.: Weight loss with AXOKINE° does not appear to be followed by rebound weight regain. Abstract. Obes. Res. (2001) 9(3).
  • SHARPE P, SMITH G: Cannabis: time for scientific evaluation of this ancient remedy? Aneth. Analg. (2000) 90(2):237–240.
  • DURST R, RUBIN-JABOTINSKY K, RASKIN S et al.: Letter to the Editor: Risperidone in Prader-Willi Syndrome. Am. Acad. Child Adolescent Psychiatr (2000) 39(5):545–546.
  • ROTHMAN RB, BAUMANN MH, SAVAGE JE et al.: Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation (2000) 102(23):2836–2841.
  • FITZGERALD LW, BURN TC, BROWN BS et al.: Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine. Mol Pharmacol (2000) 57(1):75–81.
  • GADDE KM, PARKER CB, MANER LG et al.: Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women. Obes. Res. (2000) 9:544–551.
  • SHAPIRA NA: Treatment of binge-eating disorder with topiramate: a clinical case series. J. Clin. Psychiatry (2000) 61(5)368–372.
  • FREDERIC P, DESHAIES Y, LALONDE Jet al.: Topiramate reduces energy and fat gains in lean(Fa/?) and Obese (fa/fa) Zucker Rats. Obes. Res (2000) 8:656–633.
  • PROIETTO J, FAM BC, AINSLIE DA, THORNBURN AW: Novel anti-obesity drugs. Expert Opin. Investig. Drugs (2000) 9(6):1317–1326.
  • •This is a more in depth discussion of some of the more novel anti-obesity drugs in development.
  • BOROWSKY B, DURKIN MN, OGOZOLEK K et al: Antidepressant, amdolytic and anorectic effects of a melanin-concentrating hormone - 1 receptor antagoinist. Nat. Med. (2002) 8(8):825–830.
  • WIELAND HA, HAMILTON BS, DRIST B, DOODS HN: The role of NPY in metabolic homeostasis: implications for obesity therapy. Expert Opin. Investig. Drugs (2000) 9(6):1327–1346.
  • •This is a more in depth discussion of anti-obesity drug development, focusing on NPY.
  • STROSBERG AD: Association of beta 3 adrenoceptor polymorphism with obesity and diabetes: current status. Trends Pharmacol Sci. 1997;18: 449–455.
  • FRUEBIS J: Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc. Nail Acad. ScL USA (2001) 98(4):2005–2010.
  • LEBON V, DUFOUR S, PETERSEN KF et al.: Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. J. Clin. Invest. (2001) 108:733–737.
  • HEYMSFIELD SB, GREENBERG AS, FUJIOKA D et al.: Recombinant leptin for weight loss in obese and lean adults. JAMA (1999) 282:1568–1575.
  • LUSTIG RH: The neumendoerinology ofobesity. Endocrinol Metab. Clin. 30(3):765–785.
  • MANTZOROS CS, FLIER JS: Editorial: Leptin as a therapeutic agent - trials and tribulations. J. Clin. Ednocrinol Metab. (2000) 85(11):4033–4039.
  • HUKSHORN CJ, SARIS WH, WESTERTERP-PLANTENGA MS et al.: Weekly subcutaneous pegylated recombinant native human leptin (PEG-0B) administration in obese men. J. Clin. Ednocrinol Metab. (2000) 85(11):4003–4009.
  • HUKSHORN CJ, VAN DIELEN FM, BUURMAN WA et al: The effect of pegylated recombinant human leptin (PEG-OB) on weight loss and inflammatory status in obese subjects. Int. J. Obes. Relat. Metab. Disord. (2002) 26(4):504–509.
  • PI-SUNYER FX, LAFERRERE B, ARONNE LJ, BRAY GA: Obesity, a modern day epidemic. j Clin. Endocrinol Metab. (1999) 84(1):3–12.
  • •This is a review of obesity by some of the more acknowledged experts in the field.
  • AHREN B, HOLST JJ, EFENDIC S: Andidiabetogenic action of cholecystokinin-8 in Type 2 diabetes. J. Clin. Endocrinol Metab. (2000) 85(3):1043–1048.
  • VERDICH C, FLINT A, GUTZWILLER JP et al.: A meta-analysis of the effect of glucagon-like peptide-1 (7–36) amide on ad libitum energy intake in humans.' Clin. Endocrinol Metab. (2001) 86(9):4382–4389.
  • ZANDER M: Effect of 6-week course of glucagons-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in Type 2 diabetes: a parallel-group study. Lancet (2002) 359(9309):824–830.
  • HANGSTROM-TOFT E: Action of glucagon and glucagon-like peptide. I Clin. Endocrinol Metab. (2001) 86(3):1229–1234.
  • WASAN KM, NAJAFI S, WONG J et al.: Assessing plasma lipid levels, body weight, and hepatic and renal toxicity following chronic oral administration of a water soluble phytostanol compound, FM-VP4, to gerbils. Pharm. Pharmacem. Sci (2001) 4(3):228–234.
  • CUMMINGS DE, WEIGLE DS, FRAYO RS et al.: Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. NE JM (2002) 346(21):1623–1630.
  • PASQUALI R, GAMBINERI A, BISCOTTI D: Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without polycystic ovary syndrome. Clin. Endocrinol Metab. (2000) 85(8):2767–2774.
  • MITAL A, VATS RK, RAMACHANDRAN U: PPAR's: Nuclear receptors for antidiabetics. GRIPS (2002) 3(1):5–8.
  • EDVARDSSON U, ALEXANDERSSON M, BROCKENHUSS VON LOWENHIELM H et al.: A proteome analysis of livers from obese (ob/ob) mice treated with the peroxisome proliferators WY 14,643. Electrophoresis (1999) 20(4–5):935–942.
  • WHITE JA, HIRSCH IB: Nonhypoglycemic drug reactions of agents used to treat diabetes. Endocrinol Metab. Clin. (2000) 29(4):803–811.
  • ZHOU YT, WANT ZW, HIGO M et al.: Reversing adipocyte differentiation: implications for treatment of obesity. Proc. Natl. Acad. Sci. USA (1999) 96(5):2391–2395.
  • KADOWAKI T: PPAR gamma agonists and antagonists. Nippon Yakurigaku Zasshi(2001) 118(5):321–326.
  • LUSTIG RH, ROSE SR, BURGHEN GA et al.: Hypothalamic obesity caused by cranial insult in children: Altered glucose and insulin dynamics and reversal by a somatostatin agonist. Pediatr. (1999) 135:162–168.
  • MYERS SE, CARREL AL, WHITMAN BY, ALLEN DB: Sustained benefit after 2 years of growth hormone on body composition, fat utilization, physical strength, and agility and growth in Prader-Willi syndrome. I Pedian: (2000) 137(1):43–49.
  • BERDAINIER CD, PARENTE JA JR, MCINTOSH MK: Is dehydroepiandrosterone an antiobesity agent? FASEB J. (1993) 7(5):414–419.
  • MASUZAKI H, PATTERSON J, SHINYAMA H, MORTON NM et aL: A transgenic model of visceral obesity and the metabolic syndrome. Science (2001) 294(5549):2166–2170.
  • SMITH SR, JONGE DL, PELLYMOUNTER M et al: Peripheral administration of human corticotropin-releasing hormone: a novel method to increase energy expenditure and fat oxidation in man. I Clin. Endocrinol Metab. (2001) 86(5):1991–1998.
  • THE CENTERS FOR DISEASE CONTROL AND PREVENTION: Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: US Department of Health and Human Services Interim Public Health Recommendations. MMWR (1997) 46(45) .
  • ••These are important obesity guidelines toreview in obesity drug protocol development, as well as clinical practice for patients exposed to fenfluramine or dexfenfluramine.
  • BENGEL D, ISAACS KR, HEILS A et al.: The appetite suppressant d-fenfluramine induces apoptosis in human serotonergic cells. Neuroreport (1998) 9(13):2989–2993.
  • KHAN MA, HERZOG CA, PETER JV et al.: The prevalence of cardiac valvular insufficiency assessed by transthorasic echocardiography in obese patients treated with appetite-suppressant drugs. NEJM (1998) 339(11):713–718.
  • KANCHERLA MK, SALTI HI, MULDERINK TA et al.: Echocardiographic prevalence of mitral and/or aortic regurgitation in patients exposed to either fenfluramine-phentermine combination or to dexfenfluramine. Am. Cardiol (1999) 84:1335–1338.
  • JICK H, VASILAKIS C, WEINRAUCH LA et al.: A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation. NEJM(1998) 339(11):719–724.
  • JOLLIS JG, LAND OLFO CK, KISSLO J et al.: Fenfluramine and phentermine and cardiovascular findings: effect of treatment duration on prevalence of valve abnormalities. Circulation (2000) 101(17):2071–2077.
  • LI R, SERDULA MK, WILLIAMSON DF et al.: Dose-effect of fenfluramine use on the severity of valvular heart disease among fen-phen patients with valvulopathy. bit. J. Obes. Relat. Metab. Disord. (1999) 23(9):926–928.
  • SINGH JP, EVANS JC, LEVY D et al: Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (The Framingham Heart Study). Am. Cardiol, (1999) 83:897–902.
  • GARDIN JM, SCHUMACHER D, CONSTANTINE Get aL: Valvular abnormalities and cardiovascular status following exposure to dexfenfluramine or phentermine/fenfluramine. JAMA (2000) 283(13):1738–1740.
  • BURGER AJ, SHERMAN HB, CHARLAMB MJ et al.: Treatment with phentermine-fenfluramine was associated with a low prevalence of significant valvular heart disease. I Am. Coll. Cardiol (1999) 34:1153–1158.
  • GARDIN JM, WEISSMAN NJ, LEUNG C et al.: Clinical and echocardiographic follow-up of patients previously treated with dexfenfluramine or phentermine/ fenfluramine. JAMA (2001) 286(16):2011–2014.
  • JEFFERS LA: Anethetic considerations for the new antiobesity medications. AANA (1996) 64(6):541–544.
  • RICH JM, LUCAS N, ROBERTS KW, SMITH KP: Unusual hypotension and bradycardia in a patient receiving fenfluramine, phentermine, and fluoxetime. Anethesiology (1998) 88(2).
  • WOLF AM, GOLDITZ GA: Current estimates of the economic cost of obesity in the United States. Obes. Res. (1998) 6(2):97–106.
  • •This describes the economic costs of obesity. Program (NCEP) Expert Panel on Detection,106. Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA (1993) 269:3015–3023.107.
  • STURM R: The effects of obesity, smoking, and problem drinking on chronic medical problems and health care costs. Health Aff (2002) 21(2):245–253.
  • STURM R, WELLS KB: Does obesity contribute as much to morbidity as poverty or smoking? Public Health (2001) 115:229–295.
  • •Both of the above suggest that the costs of obesity may not only rival, but exceed the monetary costs associated with other public health concerns such as cigarette smoking.
  • POSTON WS, FOREYT JP: Scientific and legal issues in fenfluramine/dexfenfluramine litigation. Tex. Med. (2000) 96(2):48–56.
  • PUHL R, BROWNELL D: Bias, discrimination, and obesity. Obes. Res. (2001) 9:788–805.
  • 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 (1998).
  • Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care (1997) 20(7):1183–1197.
  • American College of Endocrinology Consensus Statement on Guidelines for Glycemic Control. Endocrine Practice (2002) 8\(Suppl. 1).
  • Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. JAMA (1977) 237(3).
  • Joint National Committee: The 1988 report of the Joint National Committee on the detection, evaluation and treatment of high blood pressure (JNCArch Intern. Med. (1988) 148:1023–1038.
  • NATIONAL DIABETES DATA GROUP: Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance diabetes (1979) 28:1039–1057.
  • THE EXPERT PANEL: Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern. Med. 148:36–69.
  • Adult Treatment Panel II. Summary of theSecond Report of the National Education
  • Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA (2001) 285(19):2486–2497.
  • SMITH SR: The endocrinology of obesity. Endocr. Metab. Clin. (1996) 25(4):921–942.
  • FORD ES, GILES WH, DIETZ WH: Prevalence of the metabolic syndrome among109.US adults. JAMA (2002) 287:356–359.
  • ZIOTOPOULOU M, ERANI DM, HILEMANN SM et al: Unlike leptin, ciliary neurotrophic factor does not reverse the starvation-induced changes of serum corticosterone and hypothalamic110.neuropeptide levels but induces expression of hypothalamic inhibitors of leptin signaling. Diabetes (2000) 49(11):1890–1896.
  • MASSIE BM: Obesity and heart failure- risk factor or mechanism? N Eng. J. Med. (2000)111.347(5):358–359.
  • BATTERHAM RL, COWLEY MA, SMALL 112. CJ et al.: Gut hormone PYY 3–36 physiologically inhibits food intake. Nature (2002) 418:650–653.

Websites

  • http://www.iotf.org/ International Obesity TaskForce website. Accessed June 2002.
  • ••This is a very useful website for important information on obesity.
  • http://www.who.int/nut/obs.htm. Controlling the global obesity epidemic. World Health Organization (2002).
  • http://www.cdc.gov/health/default.htm Prevalence of overweight and obesity among adults. Centers for Disease Control and Prevention, USA (1999).
  • •This is a very useful website for important information on obesity.
  • www.regeneron.com The Official Website of Regeneron. Accessed June 2002.
  • http://en.sanofi-synthelabo.com/ Sanofi-Synthelabo Website. Accessed June 2002.
  • http://wwwjnj.com/home.html Johnson & Johnson Website. News from J & J Corporate (2002).
  • http://www.niddk.nih.gov/patient/SHOW/ lookahead.htm. Look AHEAD: Action for Health in Diabetes. National Institute of Diabetes and Digestive and Kidney Disease. Accessed June 2002.
  • http://www.naaso.org. The North American Association for the Study of Obesity. Accessed June 2002.
  • ••This is a very useful website for important information on obesity.
  • http://www.nhlbi.nih.gov/guidelines/obesity Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Accessed June 2002. This website describes current guidelines for obesity treatment.
  • http://www.nhlbi.nig.gov/guidelines/ hypertension/jnc6.pdf The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, an Treatment of High Blood Pressure. Accessed June 2002.
  • http://www.diabetes.org American Diabetes Association. Accessed June 2002.
  • http://cms.hha.govicoverage/8133-fffl.asp Tracking Sheet for Medicare Coverage of Obesity as an Illness. Centers for Medicare and Medicaid Services. Accessed June 2002.
  • http://www.nhlbi.nih.gov/guidelines/ cholesterol/index.htm. Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Accessed June 2002.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.