AJCN 19th International Congress of Nutrition
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American Journal of Clinical Nutrition, Vol. 71, No. 3, 844-845, March 2000
© 2000 American Society for Clinical Nutrition


Letters to the Editor

Benefits and risks of antiobesity agents

James W Anderson and Elizabeth C Konz

Metabolic Research Group, Veterans Administration Medical Center, University of Kentucky (HMR) Weight Management Program, University of Kentucky Lexington, KY

Dear Sir:

After successful weight loss, long-term weight maintenance is difficult and often not successful (1). Whereas recent studies (1, 2) indicate that long-term weight maintenance after very-low-energy diets that induce losses of >20 kg is better than after hypoenergetic diets that induce weight losses of <=13 kg (3), <30% of successful weight losers maintain a weight loss of >10% of initial weight at 5 y (1, 2). The available data clearly indicate that we need more effective approaches to enable obese individuals to make the lifestyle changes required to successfully maintain a healthier weight long term.

In controlled clinical trials, adjunctive drug therapies, are accompanied by significantly greater weight losses (47) and significantly better weight maintenance (5, 6, 8) than placebo. The editorial by Halsted (9) suggests that the long-term safety of orlistat is not well established. However, 4 published trials of orlistat in nearly 4000 patients established orlistat as the medication with the longest and largest database of any antiobesity drug (58). In addition, antiobesity agents facilitate long-term weight maintenance and lifestyle changes such as a lower fat intake (10), intake of more vegetables and fruit (1, 2, 10), and more physical activity (10); the benefits may far outweigh the potential risks. Emerging data indicate that maintenance of significant weight loss is accompanied by significant improvement in blood pressure (11), serum lipids (11), and glycemic control in diabetes (12). Maintaining even modest amounts of weight loss significantly decreases the risk of developing diabetes (13). Modest amounts of weight gain significantly increase the risk of developing coronary artery disease (14) and modest weight loss significantly reduces atherogenic risk factors (1113).

The value of orlistat for weight maintenance has been documented (5, 6, 8) as follows: 1) at 2 y of follow-up, 19% of orlistattreated and 8% of placebo-treated subjects maintain a weight loss of 10% of initial body weight, and 2) weight regain at 1 and 2 y in orlistat-treated subjects is less than half that of placebo-treated subjects (15). Sustaining weight reductions of this magnitude is associated with significant reductions in cardiovascular disease risk factors. In addition, enabling persons to maintain lower weights is usually associated with improved lifestyles (ie, decreased fat intake). Because the side effects related to orlistat use are exaggerated with high fat intakes, it seems likely that orlistat use will have adjunctive value in decreasing fat intake (15). Thus, in our assessment, the potential benefits of orlistat use as an adjunct to weight maintenance exceed the hypothetical risks.

REFERENCES

  1. Wadden TA, Frey DL. A multicenter evaluation of a proprietary weight loss program for the treatment of marked obesity: a five-year follow-up. Int J Eat Disord 1997;22:203–12.[Medline]
  2. Anderson JW, Vichitbandra S, Qian W, Kryscio RJ. Long-term weight maintenance after an intensive weight-loss program. Am J Coll Nutr 1999;18:620–7.
  3. Kramer FM, Jeffrey RW, Forster JL, Snell MK. Long-term follow-up of behavioral treatment for obesity: patterns of weight regain among men and women. Int J Obes 1989;13:123–35.[Medline]
  4. Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine produces dose-related weight loss. Obes Res 1999;7:189–98.[Medline]
  5. Sjostrom L, Rissanen A, Andersen T, et al. Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet 1998;352:167–72.[Medline]
  6. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA 1999;281:235–42.[Abstract/Free Full Text]
  7. Hollander P, Elbein S, Hirsch I, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. Diabetes Care 1998;21:1288–94.[Abstract]
  8. 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.[Abstract/Free Full Text]
  9. Halsted CH. Is blockage of pancreatic lipase the answer? Am J Clin Nutr 1999;69:1059–60 (editorial).[Free Full Text]
  10. Klem ML, Wing RR, McGuire MT, Seagle HM, Hill JO. A descriptive study of individuals successful at long-term maintenance of substantial weight loss. Am J Clin Nutr 1997;66:239–46.[Abstract/Free Full Text]
  11. Anderson JW, Brinkman-Kaplan VL, Lee H, Wood CL. Relationship of weight loss to cardiovascular risk factors in morbidly obese individuals. J Am Coll Nutr 1994;14:549–58.
  12. Wing RR, Loeske R, Epstein LH, Norwalk MP, Gooding W, Becker DV. Long-term effects of modest weight loss in type II diabetic patients. Arch Intern Med 1987;147:1749–53.[Abstract]
  13. 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.[Abstract/Free Full Text]
  14. Manson JE, Willett WC, Stampfer MJ, et al. Body weight and mortality among women. N Engl J Med 1995;333:677–85.[Abstract/Free Full Text]
  15. Anderson JW, Konz EC. Orlistat: a new generation of drugs for the treatment of obesity. Todays Therapeutic Trends 1999;17:243–55.




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