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Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials


CONTEXT: Safe and effective strategies to curb rising obesity prevalence rates are urgently needed and medications may play a more prominent role in future therapeutic regimens.

OBJECTIVE: To review systematically the long-term efficacy and safety of approved antiobesity medications.

DATA SOURCES: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Drug manufacturers and two obesity experts were contacted. No language restrictions were imposed.

STUDY SELECTION: Double-blind, randomized controlled studies of approved antiobesity medications with follow-up periods of 1 y or greater were eligible for inclusion.

DATA EXTRACTION: Two reviewers independently assessed all potentially relevant studies for inclusion and methodological quality using standardized abstraction forms.

RESULTS: A total of 11orlistat (n=6021) and three sibutramine (n=929) studies met inclusion criteria. Attrition rates averaged 33% in orlistat studies and 48% in sibutramine studies. A random effects model was used for meta-analysis. Compared to placebo, orlistat-treated patients displayed a 2.7 kg (95% CI: 2.3–3.1 kg) or 2.9% (95% CI: 2.3–3.4%) greater reduction in weight and patients on sibutramine displayed a 4.3 kg (95% CI: 3.6–4.9 kg) or 4.6% (95% CI: 3.8–5.4%) greater weight reduction after 1 y of follow-up. The number of patients achieving 10% or greater weight loss was 12% (95% CI: 8–16%) higher with orlistat and 15% (95% CI: 4–27%) higher with sibutramine compared to placebo. Orlistat caused gastrointestinal side effects and sibutramine increased blood pressure and pulse rate.

CONCLUSION: There is a relative paucity of long-term studies of antiobesity agents. In weight loss trials of 1-y duration, orlistat and sibutramine appear modestly effective in promoting weight loss. Longer, more methodologically rigourous studies that are powered to examine end points such as mortality and cardiovascular morbidity are required.

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We acknowledge the help of the following members of the Cochrane Collaboration: Drs S Norris, A Ohlsson and B Richter, and J Beyenne. In particular, Dr Norris' assistance with methodological issues and preparation of the initial draft was invaluable.

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Padwal, R., Li, S. & Lau, D. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int J Obes 27, 1437–1446 (2003).

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  • overweight
  • pharmacotherapy
  • antiobesity agents
  • sibutramine
  • orlistat

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