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

Int J Obes Relat Metab Disord. 2003 Dec;27(12):1437-46. doi: 10.1038/sj.ijo.0802475.


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 rigorous studies that are powered to examine end points such as mortality and cardiovascular morbidity are required.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-Obesity Agents / therapeutic use*
  • Cyclobutanes / therapeutic use
  • Humans
  • Lactones / therapeutic use
  • Obesity / drug therapy*
  • Orlistat
  • Randomized Controlled Trials as Topic


  • Anti-Obesity Agents
  • Cyclobutanes
  • Lactones
  • Orlistat
  • sibutramine