Meta-analysis: pharmacologic treatment of obesity

Ann Intern Med. 2005 Apr 5;142(7):532-46. doi: 10.7326/0003-4819-142-7-200504050-00012.


Background: In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used.

Purpose: To assess the efficacy and safety of weight loss medications approved by the U.S. Food and Drug Administration and other medications that have been used for weight loss.

Data sources: Electronic databases, experts in the field, and unpublished information.

Study selection: Up-to-date meta-analyses of sibutramine, phentermine, and diethylpropion were identified. The authors assessed in detail 50 studies of orlistat, 13 studies of fluoxetine, 5 studies of bupropion, 9 studies of topiramate, and 1 study each of sertraline and zonisamide. Meta-analysis was performed for all medications except sertraline, zonisamide, and fluoxetine, which are summarized narratively.

Data extraction: The authors abstracted information about study design, intervention, co-interventions, population, outcomes, and methodologic quality, as well as weight loss and adverse events from controlled trials of medication.

Data synthesis: All pooled weight loss values are reported relative to placebo. A meta-analysis of sibutramine reported a mean difference in weight loss of 4.45 kg (95% CI, 3.62 to 5.29 kg) at 12 months. In the meta-analysis of orlistat, the estimate of the mean weight loss for orlistat-treated patients was 2.89 kg (CI, 2.27 to 3.51 kg) at 12 months. A recent meta-analysis of phentermine and diethylpropion reported pooled mean differences in weight loss at 6 months of 3.6 kg (CI, 0.6 to 6.0 kg) for phentermine-treated patients and 3.0 kg (CI, -1.6 to 11.5 kg) for diethylpropion-treated patients. Weight loss in fluoxetine studies ranged from 14.5 kg of weight lost to 0.4 kg of weight gained at 12 or more months. For bupropion, 2.77 kg (CI, 1.1 to 4.5 kg) of weight was lost at 6 to 12 months. Weight loss due to topiramate at 6 months was 6.5% (CI, 4.8% to 8.3%) of pretreatment weight. With one exception, long-term studies of health outcomes were lacking. Significant side effects that varied by drug were reported.

Limitations: Publication bias may exist despite a comprehensive search and despite the lack of statistical evidence for the existence of bias. Evidence of heterogeneity was observed for all meta-analyses.

Conclusions: Sibutramine, orlistat, phentermine, probably diethylpropion, bupropion, probably fluoxetine, and topiramate promote modest weight loss when given along with recommendations for diet. Sibutramine and orlistat are the 2 most-studied drugs.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / therapeutic use*
  • Humans
  • Obesity / drug therapy*
  • Randomized Controlled Trials as Topic
  • Weight Loss


  • Anti-Obesity Agents