Discussion

Efficacy of Therapeutic Interventions for Obesity

Obesity is common and easy to screen for, poses a substantial health burden in the United States, and has treatment options. Although RCT evidence for long-term improved health with weight loss is limited, weight loss-associated changes in intermediate health variables suggest benefit. In the setting of escalating obesity prevalence, the importance of considering body weight in clinical practice seems clear.

Obese patients can achieve modest but clinically significant, sustained (1-2 years) weight loss (e.g., 3-5 kg of weight loss) with counseling. As control groups frequently received some intervention, this estimate may be conservative. More intense programs generally achieved more success, as did those incorporating behavioral therapy. Treating patients on an individual (vs group) basis appeared less important.

Sibutramine and orlistat have modest potentially prolonged effects (weight loss of 3-5.5 kg). These estimates do not reflect effects of lifestyle intervention that should accompany pharmacotherapy. Weight maintenance trials suggest that prolonged therapy with these drugs confers some benefit, but that its discontinuation may lead to rapid weight regain. Other drugs show inconsistent or short-term benefit. In both counseling and pharmacotherapy trials, a relatively high frequency of participants have achieved clinically significant (5-10 percent) weight loss.

Surgical options can promote substantial weight loss (10-159 kg over 1-5 years). Case series evidence suggests such loss can be achieved in patients with multiple comorbid conditions and may be prolonged. Although surgical options are appropriate only for the very obese, between 5 percent and 6 percent of U.S. adults have a BMI of 35 or greater,¹⁷⁹ so the number of potentially eligible persons may be substantial.

Limitations of the Literature

Limitations of prior systematic reviews included different eligibility criteria, treatment classifications, and approaches to data synthesis. In addition, aggregate values of their findings do not reflect variations in RCT sample size, length of followup, or treatment differences (e.g., counseling intensity). There was partial, but incomplete, overlap in the literature covered by each review. Overall, however, findings were consistent.

Recent primary literature likewise had deficiencies. Among counseling and pharmacotherapy trials, internal validity was typically fair (with limitations including loss to followup and differential attrition between arms), although a few were judged to have good validity. Studies tended to report mean weight change but not frequency of response. External validity was an issue: participants were frequently volunteers with limited sex and ethnic diversity. No counseling RCT was of more than 54 months duration. Pharmacotherapy trials were accepted with shorter followup periods than other treatment modes. Although 6- and 12-month efficacy appeared similar among these trials, shorter duration could inflate estimates of sustained weight loss. Surgical data were limited by lack of placebo-controlled RCT evidence; available studies often did not report response frequency, participant comorbidities, or co-interventions.

Finally, some studies (particularly pharmacotherapy ones) used a "last observation carried forward" analytic approach—the final weight outcome available was used as the final weight for those participants who dropped out of the study. Because maximal weight loss tends to occur within 6 months of intervention, this technique may overestimate the ability to sustain weight loss. Although a common technique when a true intention-to-treat analysis is not possible, it should be combined with alternate analyses.^180,181 Although many trials showed parallel analyses of trial enrollees and completers, few authors presented parallel "worst case" analyses.

Harms of Intervention

Treatment appeared reasonably safe. We identified no evidence evaluating counseling harms. Both sibutramine and orlistat had clinically significant, often mild, adverse effects in trials lasting, at most, 2 years. Surgical options clearly entail the highest risk; they lead to mortality in less than 1 percent of patients in pooled samples, but up to 25 percent of patients may need re-operation over 5 years.

A systematic review of intervention costs was beyond the scope of this project, but, notably, obesity treatment options may entail considerable cost. Intensive counseling programs require significant time and staffing commitment. Based on average U.S. wholesale price, a 1-year supply of orlistat (120 mg 3 times daily) is $1,445.40 and of sibutramine (15 mg daily) is $1464.78.¹⁸² Surgical costs reflect both the invasive procedure and long-term followup. Potentially, long-term health improvements may offset these costs to some extent.

Implications for Clinical Practice and Research

Most efficacy trials reviewed here were not carried out in clinical settings; some interventions, particularly intense counseling, may be difficult to incorporate into medical practice. One option may be referral to programs that offer intense counseling with behavioral therapy. Another may be combining office-based counseling with innovative delivery of behavioral approaches, such as video tapes or Internet-delivered adjuncts.

Other topics requiring future research include longer-term efficacy and harms followup of weight loss strategies (including better characterization of weight-cycling risks), post-marketing safety records of drugs, ability of interventions to alter body fat distribution, race and ethnic-specific health effects of purposeful reduction of central adiposity, and efficacy of weight maintenance strategies. In the interest of obesity prevention, treatment efficacy and health effects of lifestyle modification should be clarified for patients who are overweight, but not obese. Finally, better estimates of the cost-effectiveness of obesity screening and treatment, including their impact on long-term health outcomes, are needed.

Long-term research on combined treatment modalities in more generalized populations is needed. We were unable to assess treatment effectiveness by sex or ethnicity. Intervention efficacy trials have focused on white women, and observational evidence for health outcomes comes mostly from populations of European origin. Treatment efficacy may differ with race;^11,78 as certain ethnic groups have a disproportionate obesity prevalence, this area needs further attention.

All obesity therapies carry promise and burden, which must be balanced in clinical decisionmaking. Counseling approaches appear the least harmful and produce modest, clinically important weight loss, but entail cost in time and resources. Pharmacotherapy promotes modest additional weight loss, but long-term drug use may be needed to sustain this benefit with unknown long-term adverse events and appreciable cost. Only surgical options consistently result in large amounts of long-term weight reduction; however, they carry a low risk for severe complications and are expensive. Body size, health status, and prior weight loss history may all influence obesity treatment.

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Acknowledgments

This study was developed by the RTI International-University of North Carolina Evidence-based Practice Center under contract to AHRQ (Contract No. 290-97-0011), Rockville, MD. Dr. McTigue was supported by the University of North Carolina Robert Wood Johnson Clinical Scholars Program.

The authors thank David Atkins, M.D., M.P.H., Medical Officer, Center for Outcomes and Evidence, and Eve Shapiro, Managing Editor, USPSTF, AHRQ. We extend our appreciation as well to Loraine Monroe of RTI.

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References

1. National Center for Health Statistics Division of Data Services. Health, United States 2002, with Chartbook on Trends in the Health of Americans. Hyattsville, MD: National Center for Health Statistics, Division of Data Services; 2002.

2. Dietz WH. Overweight and precursors of type 2 diabetes mellitus in children and adolescents. J Pediatr 2001;138:453-4.

3. Strauss RS, Pollack HA. Epidemic increase in childhood overweight, 1986-1998. JAMA 2001;286:2845-8.

4. Ogden CL, Flegal KM, Carroll MD, Johnson CL. Prevalence and trends in overweight among US children and adolescents, 1999-2000. JAMA 2002;288:1728-32.

5. National Center for Health Statistics. Health, United States, 2001, with Urban and Rural Health Chartbook, Hyattsville, MD: National Center for Health Statistics; 2001.

6. Harwell TS, Gohdes D, Moore K, McDowall JM, Smilie JG, Helgerson SD. Cardiovascular disease and risk factors in Montana American Indians and non-Indians. Am J Prev Med 2001;20:196-201.

7. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, 2nd ed. Washington, DC: Office of Disease Prevention and Health Promotion; 1996:219-29.

8. Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA 2003;289:187-93.

9. Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med 2003;138:24-32.

10. Roe DA, Eickwort KR. Relationships between obesity and associated health factors with unemployment among low income women. J Am Med Womens Assoc 1976;31:193-4, 198-9, 203-4.

11. NHLBI Obesity Education Initiative. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the Evidence Report. Bethesda, MD . U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute. 1998; NIH Publication No. 98-4083.

12. McTigue KM, Garrett JM, Popkin BM. The natural history of the development of obesity in a cohort of young U.S. adults between 1981 and 1998. Ann Intern Med 2002;136:857-64.

13. Juhaeri, Stevens J, Chambless LE, et al. Associations between weight gain and incident hypertension in a bi-ethnic cohort: the Atherosclerosis Risk in Communities Study. Int J Obes Relat Metab Disord 2002;26:58-64.

14. Lovejoy JC, de la Bretonne JA, Klemperer M, Tulley R. Abdominal fat distribution and metabolic risk factors: effects of race. Metabolism 1996;45:1119-24.

15. Albu JB, Murphy L, Frager DH, Johnson JA, Pi-Sunyer FX. Visceral fat and race-dependent health risks in obese nondiabetic premenopausal women. Diabetes 1997;46:456-62.

16. Casas YG, Schiller BC, DeSouza CA, Seals DR. Total and regional body composition across age in healthy Hispanic and white women of similar socioeconomic status. Am J Clin Nutr 2001;73:13-8.

17. Conway JM, Yanovski SZ, Avila NA, Hubbard VS. Visceral adipose tissue differences in black and white women. Am J Clin Nutr 1995;61:765-71.

18. Dowling HJ, Pi-Sunyer FX. Race-dependent health risks of upper body obesity. Diabetes 1993;42:537-43.

19. Lear SA, Chen MM, Frohlich JJ, Birmingham CL. The relationship between waist circumference and metabolic risk factors: cohorts of European and Chinese descent. Metabolism 2002;51:1427-32.

20. Wajchenberg BL, Giannella-Neto D, Da Silva ME, Santos RF. Depot-Specific Hormonal Characteristics of Subcutaneous and Visceral Adipose Tissue and their Relation to the Metabolic Syndrome. Horm Metab Res 2002;34:616-21.

21. Park YW, Allison DB, Heymsfield SB, Gallagher D. Larger amounts of visceral adipose tissue in Asian Americans. Obes Res 2001;9:381-7.

22. Hill JO, Sidney S, Lewis CE, Tolan K, Scherzinger AL, Stamm ER. Racial differences in amounts of visceral adipose tissue in young adults: the CARDIA (Coronary Artery Risk Development in Young Adults) study. Am J Clin Nutr 1999;69:381-7.

23. Bacha F, Saad R, Gungor N, Janosky J, Arslanian SA. Obesity, regional fat distribution, and syndrome X in obese black versus white adolescents: race differential in diabetogenic and atherogenic risk factors. J Clin Endocrinol Metab 2003;88:2534-40.

24. Wolf AM, Colditz GA. Current estimates of the economic cost of obesity in the United States. Obes Res 1998;6:97-106.

25. Thompson D, Edelsberg J, Colditz GA, Bird AP, Oster G. Lifetime health and economic consequences of obesity. Arch Intern Med 1999;159:2177-83.

26. Galuska DA, Will JC, Serdula MK, Ford ES. Are health care professionals advising obese patients to lose weight? JAMA 1999;282:1576-8.

27. Harris RP, Helfand M, Woolf SH, et al. Current methods of the U.S. Preventive Services Task Force: a review of the process. Am J Prev Med 2001;20 (3 Suppl):21-35.

28. Douketis JD, Feightner JW, Attia J, Feldman WF. Periodic health examination, 1999 update: 1. Detection, prevention and treatment of obesity. Canadian Task Force on Preventive Health Care. CMAJ 1999;160:513-25.

29. NHS Centre for Reviews and Dissemination University of York. The prevention and treatment of obesity. Eff Health Care 1997;3:1-12.

30. National Task Force on the Prevention and Treatment of Obesity. Long-term pharmacotherapy in the management of obesity. JAMA 1996;276:1907-15.

31. Arterburn D, Noel PH. Effects of drug treatment for obesity in adults. Clin Evid 2001;412-19.

32. Gokcel 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;24:1957-60.

33. McNulty SJ, Ur E, Williams G. A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin. Diabetes Care 2003;26:125-31.

34. Sorkin JD, Muller D, Andres R. Body mass index and mortality in Seventh-day Adventist men. A critique and re-analysis. Int J Obes Relat Metab Disord 1994;18:752-4.

35. Manson JE, Willett WC, Stampfer MJ, et al. Body weight and mortality among women. N Engl J Med 1995;333:677-85.

36. Laara E, Rantakallio P. Body size and mortality in women: a 29 year follow up of 12,000 pregnant women in northern Finland. J Epidemiol Community Health 1996;50:408-14.

37. Shaper AG, Wannamethee SG, Walker M. Body weight: implications for the prevention of coronary heart disease, stroke, and diabetes mellitus in a cohort study of middle aged men. BMJ 1997;314:1311-7.

38. Chyou PH, Burchfiel CM, Yano K, et al. Obesity, alcohol consumption, smoking, and mortality. Ann Epidemiol 1997;7:311-7.

39. Wannamethee SG, Shaper AG, Walker M, Ebrahim S. Lifestyle and 15-year survival free of heart attack, stroke, and diabetes in middle-aged British men. Arch Intern Med 1998;158:2433-40.

40. Huang Z, Willett WC, Manson JE, et al. Body weight, weight change, and risk for hypertension in women. Ann Intern Med 1998;128:81-8.

41. Durazo-Arvizu RA, McGee DL, Cooper RS, Liao Y, Luke A. Mortality and optimal body mass index in a sample of the US population. Am J Epidemiol 1998;147:739-49.

42. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999;341:1097-105.

43. Rosengren A, Wedel H, Wilhelmsen L. Body weight and weight gain during adult life in men in relation to coronary heart disease and mortality. A prospective population study. Eur Heart J 1999;20:269-77.

44. Folsom AR, Kushi LH, Anderson KE, et al. Associations of general and abdominal obesity with multiple health outcomes in older women: the Iowa Women's Health Study. Arch Intern Med 2000;160:2117-28.

45. Song YM, Sung J. Body mass index and mortality: a twelve-year prospective study in Korea. Epidemiology 2001;12:173-9.

46. Allison DB, Moonseong H, Fontaine KR, Hoffman DJ. Body Weight, body composition and longevity. In: Bojorntorp P, ed. International Textbook of Obesity. New York: J Wiley; 2001: 31-48.

47. Kim KS, Owen WL, Williams D, Adams-Campbell LL. A comparison between BMI and Conicity index on predicting coronary heart disease: the Framingham Heart Study. Ann Epidemiol 2000;10:424-31.

48. Nilsen TI, Vatten LJ. Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis. British Journal of Cancer 2001;84:417-22.

49. Stevens J. Obesity and mortality in Africans-Americans. Nutr Rev 2000;58(11):346-53.

50. Heiat A, Vaccarino V, Krumholz HM. An evidence-based assessment of federal guidelines for overweight and obesity as they apply to elderly persons. Arch Intern Med 2001;161:1194-203.

51. Deurenberg P, Weststrate JA, Seidell JC. Body mass index as a measure of body fatness: age- and sex-specific prediction formulas. Br J Nutr 1991;65:105-14.

52. Gray DS, Fujioka K. Use of relative weight and Body Mass Index for the determination of adiposity. J Clin Epidemiol 1991;44:545-50.

53. Wang J, Thornton JC, Russell M, Burastero S, Heymsfield S, Pierson RN Jr. Asians have lower body mass index (BMI) but higher percent body fat than do whites: comparisons of anthropometric measurements. Am J Clin Nutr 1994;60:23-28.

54. Deurenberg P, Yap M, van Staveren WA. Body mass index and percent body fat: a meta analysis among different ethnic groups. Int J Obes Relat Metab Disord 1998;22:1164-71.

55. Gurrici S, Hartriyanti Y, Hautvast JG, Deurenberg P. Relationship between body fat and body mass index: differences between Indonesians and Dutch Caucasians. Eur J Clin Nutr 1998;52:779-83.

56. Deurenberg P, van der Kooy K, Hulshof T, Evers P. Body mass index as a measure of body fatness in the elderly. Eur J Clin Nutr 1989;43:231-6.

57. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:481-6.

58. Rexrode KM, Carey VJ, Hennekens CH, et al. Abdominal adiposity and coronary heart disease in women. JAMA 1998;280:1843-8.

59. Liese AD, Mayer-Davis EJ, Tyroler HA, et al. Development of the multiple metabolic syndrome in the ARIC cohort: joint contribution of insulin, BMI, and WHR. Atherosclerosis risk in communities. Ann Epidemiol 1997;7:407-16.

60. Baik I, Ascherio A, Rimm EB, et al. Adiposity and mortality in men. Am J Epidemiol 2000;152:264-71.

61. Janssen I, Katzmarzyk PT, Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch Intern Med 2002;162:2074-9.

62. Eden KB, Orleans CT, Mulrow CD, Pender NJ, Teutsch SM. Does counseling by clinicians improve physical activity? A summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:208-15.

63. U.S. Department of Health and Human Services. Physical Activity and Health: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion; 1996. Available at: http://www.cdc.gov/nccdphp/sgr/pdf/sgrfull.pdf. Accessed July 23, 2003.

64. Stevens J, Cai J, Evenson KR, Thomas R. Fitness and fatness as predictors of mortality from all causes and from cardiovascular disease in men and women in the lipid research clinics study. Am J Epidemiol 2002;156:832-41.

65. Wadden TA, Berkowitz RI, Sarwer DB, Prus-Wisniewski R, Steinberg C. Benefits of lifestyle modification in the pharmacologic treatment of obesity: a randomized trial. Arch Intern Med 2001;161:218-27.

66. Kuller LH, Simkin-Silverman LR, Wing RR, Meilahn EN, Ives DG. Women's Healthy Lifestyle Project: A randomized clinical trial: results at 54 months. Circulation 2001;103:32-7.

67. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343-50.

68. Rothacker DQ, Staniszewski BA, Ellis PK. Liquid meal replacement vs traditional food: a potential model for women who cannot maintain eating habit change. J Am Diet Assoc 2001;101:345-7.

69. Jones DW, Miller ME, Wofford MR, et al. The effect of weight loss intervention on antihypertensive medication requirements in the Hypertension Optimal Treatment (HOT) study. Am J Hypertens 1999;12:1175-80.

70. Stevens VJ, Obarzanek E, Cook NR, et al. Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II. Ann Intern Med 2001;134:1-11.

71. Swinburn BA, Woollard GA, Chang EC, Wilson MR. Effects of reduced-fat diets consumed ad libitum on intake of nutrients, particularly antioxidant vitamins. J Am Diet Assoc 1999;99:1400-5.

72. Jakicic JM, Winters C, Lang W, Wing RR. Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, and fitness in overweight women: a randomized trial. JAMA 1999;282:1554-60.

73. Leermakers EA, Perri MG, Shigaki CL, Fuller PR. Effects of exercise-focused versus weight-focused maintenance programs on the management of obesity. Addict Behav 1999;24:219-27.

74. Sbrocco T, Nedegaard RC, Stone JM, Lewis EL. Behavioral choice treatment promotes continuing weight loss: preliminary results of a cognitive-behavioral decision-based treatment for obesity. J Consult Clin Psychol 1999;67:260-6.

75. Fogelholm M, Kukkonen-Harjula K, Oja P. Eating control and physical activity as determinants of short-term weight maintenance after a very-low-calorie diet among obese women. Int J Obes Relat Metab Disord 1999;23:203-10.

76. Fogelholm M, Kukkonen-Harjula K, Nenonen A, Pasanen M. Effects of walking training on weight maintenance after a very-low-energy diet in premenopausal obese women: a randomized controlled trial. Arch Intern Med 2000;160:2177-84.

77. Jeffery RW, French SA. Preventing weight gain in adults: design, methods and one year results from the Pound of Prevention study. Int J Obes Relat Metab Disord 1997;21:457-64.

78. Wing RR, Anglin K. Effectiveness of a behavioral weight control program for blacks and whites with NIDDM. Diabetes Care 1996;19:409-13.

79. Lindholm LH, Ekbom T, Dash C, Eriksson M, Tibblin G, Schersten B. The impact of health care advice given in primary care on cardiovascular risk. CELL Study Group. BMJ 1995;310:1105-9.

80. Imperial Cancer Research Fund OXCHECK Study Group. Effectiveness of health checks conducted by nurses in primary care: final results of the OXCHECK study. BMJ 1995;310:1099-104.

81. 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.

82. Ashley JM, St Jeor ST, Schrage JP, et al. Weight control in the physician's office. Arch Intern Med 2001;161:1599-604.

83. Bemelmans WJ, Broer J, de Vries JH, Hulshof KF, May JF, Meyboom-De Jong B. Impact of Mediterranean diet education versus posted leaflet on dietary habits and serum cholesterol in a high risk population for cardiovascular disease. Public Health Nutr 2000;3:273-83.

84. James WP, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 2000;356:2119-25.

85. Dujovne CA, Zavoral JH, Rowe E, Mendel CM; The Silbutramine Study Group. 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;142:489-97.

86. 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. Diabetes Obes Metab 2000;2:175-87.

87. Smith IG, Goulder MA; On behalf of the Members of the Sibutramine Clinical Study 1047 Team. Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity. J Fam Pract 2001;50:505-12.

88. Wirth A, Krause J. Long-term weight loss with sibutramine: a randomized controlled trial. JAMA 2001;286:1331-9.

89. 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. Orlistat Dose-Ranging Study Group. Eur J Clin Pharmacol 1998;54:125-32.

90. Miles JM, Leiter L, Hollander P, et al. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diabetes Care 2002;25:1123-8.

91. Muls E, Kolanowski J, Scheen A, Van Gaal L; ObelHyx Study Group. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study. Int J Obes 2001;25:1713-21.

92. Hill JO, Hauptman J, Anderson JW, et al. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Am J Clin Nutr 1999;69:1108-16.

93. Karhunen L, Franssila-Kallunki A, Rissanen P, et al. Effect of orlistat treatment on body composition and resting energy expenditure during a two-year weight-reduction programme in obese Finns. Int J Obes Relat Metab Disord 2000;24:1567-72.

94. Micic D, Ivkovic-Lazar T, Dragojevic R, Jorga J, Stokic E, Hajdukovic Z. Orlistat, a gastrointestinal lipase inhibitor, in therapy of obesity with concomitant hyperlipidemia. Med Pregl 1999;52:323-33.

95. Rissanen P, Vahtera E, Krusius T, Uusitupa M, Rissanen A. Weight change and blood coagulability and fibrinolysis in healthy obese women. Int J Obes Relat Metab Disord 2001;25:212-8.

96. Broom I, Wilding J, Stott P, Myers N. Randomised trial of the effect of orlistat on body weight and cardiovascular disease risk profile in obese patients: UK Multimorbidity Study. Int J Clin Pract 2002;56:494-9.

97. Giugliano D, Quatraro A, Consoli G, et al. Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors. Eur J Clin Pharmacol 1993;44:107-12.

98. Gokcel A, Gumurdulu Y, Karakose H, et al. Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. Diabetes Obes Metab 2002;4:49-55.

99. Hubbard VS, Hall WH. Gastrointestinal surgery for severe obesity. Obes Surg 1991;1(3):257-65.

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