Benefits and risks of antiobesity agents

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 (4–7) 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 (5–8). 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 (11–13).

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.

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